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PubMed2000

An unusual structure formed by antisense-target RNA binding involves an extended kissing complex with a four-way junction and a side-by-side helical alignment.

The antisense RNA CopA binds to the leader region of the repA mRNA (target: CopT). Previous studies on CopA-CopT pairing in vitro showed that the dominant product of antisense RNA-mRNA binding is not a full RNA duplex. We have studied here the structure of CopA-CopT complex, combining chemical and enzymatic probing and computer graphic modeling. CopI, a truncated derivative of CopA unable to bind CopT stably, was also analyzed. We show here that after initial loop-loop interaction (kissing), helix propagation resulted in an extended kissing complex that involves the formation of two intermolecular helices. By introducing mutations (base-pair inversions) into the upper stem regions of CopA and CopT, the boundaries of the two newly formed intermolecular helices were delimited. The resulting extended kissing complex represents a new type of four-way junction structure that adopts an asymmetrical X-shaped conformation formed by two helical domains, each one generated by coaxial stacking of two helices. This structure motif induces a side-by-side alignment of two long intramolecular helices that, in turn, facilitates the formation of an additional intermolecular helix that greatly stabilizes the inhibitory CopA-CopT RNA complex. This stabilizer helix cannot form in CopI-CopT complexes due to absence of the sequences involved. The functional significance of the three-dimensional models of the extended kissing complex (CopI-CopT) and the stable complex (CopA-CopT) are discussed.

Bacterial Proteins↗

PubMed2001

An extended structural signature for the tRNA anticodon loop.

Anticodon hairpins are structural motifs with contradictory functions. The recognition by aminoacyl synthetases implies extended interactions with the anticodon base triplet and thus, usually, an unfolding of the anticodon loop. The recognition by the ribosome and cognate interaction with a mRNA codon implies, on the other hand, the formation of a mini-helix with a canonical anticodon hairpin structure as observed by crystallography and NMR. To be able to understand the various properties of this motif, a precise description of its structural conservation is required. Here, on the basis of phylogenetic, structural, and molecular dynamics data, we discuss a conserved interaction established between the ribose of the U33 and the base at position 35, either a purine or a pyrimidine. This interaction involves the hydrogen bonding donor or acceptor potential of the hydroxyl group of U33 and has to be integrated in an extended definition of the anticodon hairpin. The extended structural signature provides also an explanation for the role played by pseudouridines at position 35.

Anticodon↗

PubMed2005

Integrated light collimating system for extended optical-path-length absorbance detection in microchip-based capillary electrophoresis.

We have developed an integrated light collimating system with a microlens and a pair of slits for extended optical path length absorbance detection in a capillary electrophoresis (CE) microchip. The collimating system is made of the same material as the chip, poly(dimethylsiloxane) (PDMS), and it is integrated into the chip during the molding of the CE microchannels. In this microchip, the centers of an extended 500-microm detection cell and two optical fibers are self-aligned, and a planoconvex microlens (r = 50 microm) for light collimation is placed in front of a light-delivering fiber. To block stray light, two rectangular apertures, realized by a specially designed three-dimensional microchannel, are made on each end of the detection cell. In comparison to conventional extended detection cell having no collimator, the percentage of stray radiation readout fraction in the collimator integrated detection cell is significantly reduced from 31.6 to 3.8%. The effective optical path length is increased from 324 to 460 microm in the collimator integrated detection cell. The detection sensitivity is increased by 10 times in the newly developed absorbance detection cell as compared to an unextended, 50-microm-long detection cell. The concentration detection limit (S/N = 3) for fluorescein in the collimator integrated detection cell is 1.2 microM at the absorbance detection limit of 0.001 AU.

Journal Article↗

PubMed2005

Small amphiphilic organics, coordination extended solids, and constant curvature structures.

In this Account, we explore the role constant curvature structures play in amphiphilic small molecule crystals and extended coordination solids. A constant curvature structure is one in which there is a surface or interface that has the same curvature throughout its surface. Simple examples of such structures contain spheres (micelles), columns, or layers. Yet another family are cubic as is found in the gyroid topology. For amphiphilic systems, there are two domains, one generally hydrophobic and the other hydrophilic. We find that the interfaces between these two domains in small molecule structures resemble those in larger scale systems and adopt topologies related to constant curvature structures. The hydrophobic-to-total volume ratio, a molecular parameter, can be used to predict which type of constant curvature structure is adopted. In the case of three coordinate extended solids, constant curvature plays a role both in the extended net topology and in the hydrophobic-to-hydrophilic interface.

Journal Article↗

PubMed2000

Proximity relationships between residue 6 of troponin I and residues in troponin C: further evidence for extended conformation of troponin C in the troponin complex.

Skeletal muscle troponin C (TnC) adopts an extended conformation when crystallized alone and a compact one when crystallized with an N-terminal troponin I (TnI) peptide, TnI(1-47) [Vassylyev et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 4847-4852]. The N-terminal region of TnI (residues 1-40) was suggested to play a functional role of facilitating the movement of TnI's inhibitory region between TnC and actin [Tripet et al. (1997) J. Mol. Biol. 271, 728-750]. To test this hypothesis and to investigate the conformation of TnC in the intact troponin complex and in solution, we attached fluorescence and photo-cross-linking probes to a mutant TnI with a single cysteine at residue 6. Distances from this residue to residues of TnC were measured by the fluorescence resonance energy transfer technique, and the sites of photo-cross-linking in TnC were determined by microsequencing and mass spectrometry following enzymatic digestions. Our results show that in the troponin complex neither the distance between TnI residue 6 and TnC residue 89 nor the photo-cross-linking site in TnC, Ser133, changes with Ca(2+), in support of the notion that this region plays mainly a structural rather than a regulatory role. The distances to residues 12 and 41 in TnC's N-domain are both considerably longer than those predicted by the crystal structure of TnC.TnI(1-47), supporting an extended rather than a compact conformation of TnC. In the binary TnC.TnI complex and the presence of Ca(2+), Met43 in TnC's N-domain was identified as the photo-cross-linking site, and multiple distances between TnI residue 6 and TnC residue 41 were detected. This was taken to indicate increased flexibility in TnC's central helix and that TnC dynamically changes between a compact and an extended conformation when troponin T (TnT) is absent. Our results further emphasize the difference between the binary TnC.TnI and the ternary troponin complexes and the importance of using intact proteins in the study of structure-function relationships of troponin.

Animals↗

PubMed1987

Synthesis and biological activity of amino terminus extended analogues of the alpha mating factor of Saccharomyces cerevisiae.

The synthesis and biological activity are reported for extended analogues of the secreted tridecapeptide alpha-factor (Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr) from Saccharomyces cerevisiae. Peptides with Ala, Glu-Ala, Ala-Glu-Ala, or Glu-Ala-Glu-Ala attached to the amino terminus of alpha-factor were synthesized by the solid-phase method on a (phenylacetamido)methyl (PAM) resin, using a combination of dicyclohexylcarbodiimide- and 1-hydroxybenzotriazole-accelerated active ester coupling procedures. Free peptides were obtained by hydrogen fluoride (HF) cleavage in the presence of appropriate scavengers. Normal high HF cleavage and "low-high" HF cleavage were equally effective in liberating the desired product from the PAM resin. Yields of pure peptide ranged from 9% to 17%. All of the extended alpha-factors, which represent sequences of pro-alpha-factor coded for in the MF alpha 1 structural gene, caused morphological aberrations (shmoo assay) in strain X2180-1A (MATa) the same as those caused by the tridecapeptide. The 14-peptide was equally active compared to the native alpha-factor whereas the 17-peptide was 5-10-fold less active. The analogues also arrested to various degrees (halo assay) the growth of S. cerevisiae RC629 (MATa sst1) and S. cerevisiae RC631 (MATa sst2), two supersensitive mutants, and were converted to pheromones of equal activity by treatment with V8 protease. A temperature-sensitive receptor mutant responded to all the peptides at the permissive but not the restrictive temperature. An alpha-factor antagonist, des-Trp1,Ala3-alpha-factor, inhibited activity of all extended peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2003

Quantitative analysis of loading and extender acyltransferases of modular polyketide synthases.

The acyltransferase (AT) domains of modular polyketide synthases (PKSs) are the primary determinants of building block specificity in polyketide biosynthesis and are therefore attractive targets for protein engineering. Thus far, investigations into the fundamental biochemical properties of AT domains have been hampered by the inability to produce these enzymes as self-standing polypeptides. Here we describe an alternative, generally applicable strategy for overexpression and analysis of AT domains from modular PKSs as truncated didomain proteins (approximately 60 kDa). Recently, we reported the expression and reconstitution of the loading didomain of 6-deoxyerythronolide B synthase (Lau, J., Cane, D. E., and Khosla, C. (2000) Biochemistry 39, 10514-20). By replacing the AT domain of this protein with a methylmalonyl-CoA specific AT domain from module 6 of the 6-deoxyerythronolide B synthase, or alternatively a malonyl-CoA specific AT domain from module 2 of the rapamycin synthase, each of these extender unit AT domains could be overproduced and purified to homogeneity. Using acyl-CoA substrates as acyl group donors and N-acetylcysteamine as the thiol acceptor, we devised a steady-state kinetic assay to probe the properties of these three didomain proteins and selected mutants. Propionyl-CoA was the preferred substrate of the loading didomain, although acetyl- and butyryl-CoA were also accepted with approximately 40-fold-lower specificity. In contrast to the relatively relaxed specificity of the loading AT domain, the methylmalonyl- and malonyl-specific AT domains had high specificity (>1000-fold) toward their natural substrates. The acyl transfer reaction was inhibited by coenzyme A (CoASH) with both a competitive and a noncompetitive component. Use of an exogenous holo-acyl carrier protein (ACP) as an acceptor thiol did not increase the rate of acyl transfer relative to the reaction involving N-acetylcysteamine, suggesting that either the on-rate of the acyl group is rate-limiting or that the apo-ACP component of the didomain protein precludes effective docking of a second ACP onto the AT active site. Mutation of Trp-222 in the loading AT domain to an Arg residue that is universally conserved in all extender unit AT domains failed to enable the loading AT domain to accept methylmalonyl-CoA as an alternative substrate. In contrast, mutation of the equivalent Arg residue in an extender AT domain resulted in a protein with no activity. Together, these results provide a foundation for future structural and mechanistic investigations into the properties of AT domains of modular PKSs.

Acetyl Coenzyme A↗

PubMed2003

Variants of DNA polymerase Beta extend mispaired DNA due to increased affinity for nucleotide substrate.

DNA polymerase beta offers an attractive system to study the biochemical mechanism of polymerase-dependent mutagenesis. Variants of DNA polymerase beta, Y265F and Y265W, were analyzed for misincorporation efficiency and mispair extension ability, relative to wild-type DNA polymerase beta. Our data show that the fidelity of the mutant polymerases is similar to wild-type enzyme on a one-nucleotide gapped DNA substrate. In contrast, with a six-nucleotide gapped DNA, the mutant proteins are slightly more accurate than the wild-type enzyme. The mutagenic potential of Y265F and Y265W is more pronounced when encountering a mispaired DNA substrate. Here, both variants can extend a G:G mispair quite efficiently, and Y265F can also extend a T:G mispair. The kinetic basis of the increased mispair extension efficiency is due to an improved ability to bind to the incoming nucleotide. Y265W extends the G:G mispair even with an incorrect nucleotide substrate. Overall, our results demonstrate that the Y265 hinge residue is important for stabilizing the architecture of the nucleotide binding pocket of DNA polymerase beta, and that alterations of this residue can have significant impacts upon the fidelity of DNA synthesis.

Amino Acid Substitution↗

PubMed1998

Human cytomegalovirus protease complexes its substrate recognition sequences in an extended peptide conformation.

Substrate hydrolysis by human cytomegalovirus (HCMV) protease is essential to viral capsid assembly. The interaction of HCMV protease and the N-terminal cleavage products of the hydrolysis of R- and M-site oligopeptide substrate mimics (R and M, respectively, which span the P9-P1 positions) was studied by NMR methods. Protease-induced differential line broadening indicated that ligand binding is mediated by the P4-P1 amino acid residues of the peptides. A well-defined extended conformation of R from P1 through P4 when complexed to HCMV protease was evidenced by numerous transferred nuclear Overhauser effect (NOE) correlations for the peptide upon addition of the enzyme. NOE cross-peaks between the P4 and P5 side chains placing these two groups in proximity indicated a deviation from the extended conformation starting at P5. Similar studies carried out for the M peptide also indicated an extended peptide structure very similar to that of R, although the conformation of the P5 glycine could not be established. No obvious variation in structure between bound R and M (notably at P4, where the tyrosine of the R-site has been suggested to play a key role in ligand binding) could be discerned that might explain the observed differences in processing rates between R- and M-sequences. Kinetic studies, utilizing R- and M-site peptide substrates for which the P5 and P4 residues were separately exchanged, revealed that these positions had essentially no influence on the specificity constants (kcat/KM). In sharp contrast, substitution of the P2 residue of an M-site peptide changed its specificity constant to that of an R-site peptide substrate, and vice versa.

Amino Acid Substitution↗

PubMed1998

Rabbit beta-globin is extended beyond its UGA stop codon by multiple suppressions and translational reading gaps.

Translational reading gaps occur when genetic information encoded in mRNA is not translated during the normal course of protein synthesis. This phenomenon has been observed thus far only in prokaryotes and is a mechanism for extending the reading frame by circumventing the normal stop codon. Reading frames of proteins may also be extended by suppression of the stop codon mediated by a suppressor tRNA. The rabbit beta-globin read-through protein, the only known, naturally occurring read-through protein in eukaryotes, was sequenced by ion trap mass spectrometry to determine how the reading frame is extended. Seven different proteolytic peptide fragments decoded by the same sequence that spans the UGA stop codon of rabbit beta-globin mRNA were detected. Three of these peptides contain translational reading gaps of one to three amino acids that correspond to the UGA stop codon site and/or one or two of the immediate downstream codons. To our knowledge, this is the first reported example of the occurrence of reading gaps in protein synthesis in eukaryotes. This event is unique in that it is associated with bypasses involving staggered lengths of untranslated information. Four of the seven peptides contain serine, tryptophan, cysteine, and arginine decoded by UGA and thus arise by suppression. Serine is donated by selenocysteine tRNA, and it, like the other tRNAs, has previously been shown to suppress UGA in vitro in mammals, but not in vivo.

Amino Acid Sequence↗

PubMed1999

Troponin I inhibitory peptide (96-115) has an extended conformation when bound to skeletal muscle troponin C.

We have utilized CD and NMR spectroscopy to study the conformation of the troponin I (TnI) inhibitory peptide [TnI(96-115)] free in solution and when bound to troponin C (TnC). Analysis of the CD spectrum of the free peptide in aqueous solution indicates it is only approximately 3% helix. Upon complex formation with TnC, there is no change in total helix content compared to the sum of the free components. The NMR data support a predominantly extended conformation for the free peptide. TnI(96-115) bound to TnC was selectively observed by NMR using deuterated TnC (dTnC). For the 1:1 ratio of TnI(96-115) to dTnC used, 95% of the peptide was bound to dTnC. The chemical shifts of the TnC-bound peptide resonances are similar to those of the free peptide, indicating that the change in peptide conformation as a consequence of binding to TnC is small. For the TnC-bound TnI(96-115) peptide, the ratios of sequential Halpha-HN to intraresidue HN-Halpha NOE cross-peak volumes support a predominantly extended conformation, possibly kinked at Gly104. The results presented here are in agreement with sequence analysis predictions for TnI(96-115) as a free peptide or within the intact TnI sequence. The predominantly extended structure for the 96-115 inhibitory sequence segment of TnI with a kink at Gly104 may facilitate its binding alternately to actin or TnC in response to the Ca2+ signals that control thick and thin filament interactions during the contractile cycle.

Amino Acid Sequence↗

PubMed2000

The region of antithrombin interacting with full-length heparin chains outside the high-affinity pentasaccharide sequence extends to Lys136 but not to Lys139.

The interaction of a well-defined pentasaccharide sequence of heparin with a specific binding site on antithrombin activates the inhibitor through a conformational change. This change increases the rate of antithrombin inhibition of factor Xa, whereas acceleration of thrombin inhibition requires binding of both inhibitor and proteinase to the same heparin chain. An extended heparin binding site of antithrombin outside the specific pentasaccharide site has been proposed to account for the higher affinity of the inhibitor for full-length heparin chains by interacting with saccharides adjacent to the pentasaccharide sequence. To resolve conflicting evidence regarding the roles of Lys136 and Lys139 in this extended site, we have mutated the two residues to Ala or Gln. Mutation of Lys136 decreased the antithrombin affinity for full-length heparin by at least 5-fold but minimally altered the affinity for the pentasaccharide. As a result, the full-length heparin and pentasaccharide affinities were comparable. The reduced affinity for full-length heparin was associated with the loss of one ionic interaction and was caused by both a lower overall association rate constant and a higher overall dissociation rate constant. In contrast, mutation of Lys139 affected neither full-length heparin nor pentasaccharide affinity. The rate constants for inhibition of thrombin and factor Xa by the complexes between antithrombin and full-length heparin or pentasaccharide were unaffected by both mutations, indicating that neither Lys136 nor Lys139 is involved in heparin activation of the inhibitor. Together, these results show that Lys136 forms part of the extended heparin binding site of antithrombin that participates in the binding of full-length heparin chains, whereas Lys139 is located outside this site.

Antithrombins↗

PubMedDate not supplied

In vitro hydrolysis of poly(l-lactide) crystalline residues as extended-chain crystallites: II. Effects of hydrolysis temperature.

The effects of hydrolysis temperature on the hydrolysis behavior and mechanism of poly(l-lactide) crystalline residues or extended-chain crystallites were investigated in phosphate-buffered solution (50-97 degrees C), using gel permeation chromatography and differential scanning calorimetry (DSC). The hydrolysis of the crystalline residues proceeded from their surface composed of very short chains with a free end along the chain direction, irrespective of hydrolysis temperature, but the hydrolysis from their lateral surface could not be traced. The activation energy of hydrolysis for the crystalline residues (extended-chain crystallites) was evaluated to be 18.0 kcal mol(-1) (75.2 kJ mol(-1)). The monotonic melting temperature (T(m)) and crystallinity decreases occurred after their initial very small increases, excluding the monotonic crystallinity decrease at 97 degrees C with no initial increase. The T(m) decrease reflects the decreased thickness of the crystalline residues. The equilibrium T(m) of the crystalline residues (extended-chain crystallites) was estimated to be 464.5-464.9 K. The free energy values for the surface composed of very short chains with a free end, which are neighboring the air (or nitrogen during DSC scanning), were calculated to be 55.6-56.4 erg cm(-2) for heat of fusion per unit mass = 135 J g(-1). The obtained surface free energy values are significantly higher than that for the surface composed of folding chains, tie chains, and the chains with a free end, which are neighboring the same kind of amorphous chains (39.9 erg cm(-2)).

Calorimetry, Differential Scanning↗

PubMed2004

Nanohybrids from liquid crystalline extended amphiphilic dendrimers.

A novel extended amphiphilic dendrimer with linear poly(ethylene oxide) (PEO) attached to a PEO-like dendritic core as hydrophilic fraction and eight docosyl chain branches as hydrophobic fraction has been prepared for the use as structure-directing agent for silica-type materials. The extended dendrimer exhibits a hexagonal columnar liquid crystalline phase in the melt. Organically modified inorganic precursors and the extended dendrimer co-assemble into nanostructured hybrids. Hybrids with 0.44 weight fraction (fw) of aluminosilicate show a lamellar morphology, while hybrids with 0.21 fw exhibit a cylindrical structure. Nanostructures were characterized by a combination of small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The results suggest that dendrimer-based amphiphiles may provide an exciting platform for the formation of multifunctional organic-inorganic nanostructured hybrid materials with unique structural characteristics.

Journal Article↗

PubMed2006

Effect of extended aging of parma dry-cured ham on the content of oligopeptides and free amino acids.

The effect of the dry-curing processing time on the release of oligopeptides and amino acids was evaluated with 158 Parma hams subdivided into three groups: (1) traditional processing (450 days); (2) extended processing (570 days); and (3) extended aging (690 days). Most of the oligopeptides and free amino acids detected increased up to the last deadline (690 days); a sharp increase of peptides below 400 Da was the main change in most aged hams. In particular, gamma-glutamyl dipeptides showed a remarkable increase during ham extended aging, acting like permanent taste-active compounds, being unsuitable for further enzymatic breakdown. The pH of fresh hams showed negative relationships (P < 0.001) with most peptides. With regard to free amino acids, the pattern was modified by different processing lengths, together with their taste categories, so that the amino acids having monosodium glutamate-like and bitter tastes were enhanced in more aged hams.

Amino Acids↗

PubMed2004

Chemometric studies on the bactericidal activity of quinolones via an extended VolSurf approach.

An extended VolSurf approach, that additionally includes SHAPE descriptors, was applied to a dataset of 55 quinolones. Bactericidal activity was measured at Bayer AG, Germany, for Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis). Chemometric analysis was first approached via a classical VolSurf approach. The following descriptors were found most important: bactericidal activity particularly increases with high values of the best volume (BV11(OH2)) and the minimum energy (Emin1(OH2)) of the water probe, high values of the integy moment (ID(DRY)) of the lipophilic probe, and high values of the hydrophilic region (W(O)) of the hydrogen bond acceptor probe. Best volume (BV31(OH2)) of the water probe and best volume (BV12(DRY)) and lipophilic regions (D(DRY)) of the lipophilic probe as well as H-bonding capacity derived with the CO probe (HB(O)) are inversely related to activity. PLS analysis yields a five-component model with an r(2) of 0.83 and a q(2) of 0.43 after variable selection via fractional factorial design (FFD). Chemometric modeling could be improved by including newly derived SHAPE descriptors, which were merged with the VolSurf descriptors and subjected to PLS analysis. The global model of this extended VolSurf approach is optimal with two components and exhibits a significantly improved statistical quality; a marginally reduced r(2) (0.75 versus 0.83) is more than compensated by a highly improved predictivity with a q(2) of 0.63 versus 0.43. To prove model quality, external prediction of seven test set quinolones was performed. The precise prediction of all test set molecules nicely demonstrates the robustness and statistical significance of the obtained chemometric model using the extended VolSurf approach.

Anti-Bacterial Agents↗

PubMed2001

Neural-specific overexpression of drosophila plenty of SH3s (DPOSH) extends the longevity of adult flies.

Extended longevity mutants are extremely useful to understand the molecular mechanism of longevity determination. Here we report identification and characterization of the Drosophila Plenty of SH3s (DPOSH) gene, a candidate that might be associated with the extended longevity phenotype. DPOSH encodes a protein containing a RING finger domain and four SH3 domains. We showed that neural-specific overexpression of DPOSH could extend the mean longevity of adult flies by 14% at 25 degrees C without affecting viability or morphology. In contrast, forced expression of DPOSH in developing imaginal discs produced various phenotypes including lethality and morphological defects such as loss of crossvein, notched wing, and disordered hair polarity. Puckered, a target gene of JNK/SAPK pathway, was activated by overexpression of DPOSH and the forced expression phenotypes were suppressed by introducing a mutation of Drosophila JNK (bsk) or JNKK (hep), suggesting that the JNK/SAPK signaling pathway is one of the critical elements in the determination of longevity.

Adaptor Proteins, Signal Transducing↗

PubMed1992

Correlation of in vitro release rate and in vivo absorption characteristics of four chlorpheniramine maleate extended-release formulations.

An in vitro/in vivo correlation was established for four formulations of chlorpheniramine maleate (histamine, H1-blocker) extended-release tablets exhibiting different in vitro release rate characteristics. In vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2, paddle stirrer at 50 rpm in 1000 ml of distilled water at 37.0 +/- 0.5 degrees C. Inspection of the individual and mean release rate data indicated that the in vitro release rate of chlorpheniramine maleate was consistent with the intended design of the four extended-release formulations. The in vivo bioavailability and pharmacokinetics of these formulations were evaluated in 24 healthy subjects under fasting conditions. Wagner Nelson analyses of the in vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in vitro release resulted in a statistically significant correlation (r2 greater than 0.98, P less than 0.001) for each formulation. Qualitative rank-order correlations were observed among all combinations of in vitro and in vivo parameters. These data support a Level A correlation between the in vitro release rate profiles and the in vivo absorption for chlorpheniramine maleate determined under fasting conditions.

Adult↗