Biomedical subjects

M Bienert

Publications and source records attributed to M Bienert.

At least 55 records · Page 3Linked to original sources

PubMed1997

Hydrophobically induced conformation in ovine corticotropin-releasing hormone.

Multiple peptide synthesis has been applied for the simultaneous synthesis of systematic replacement sets of model peptides which varied in length from 18 to 36 residues and ovine corticotropin-releasing hormone (oCRH), a 41-residue receptor-binding peptide. The peptides were utilized to analyze the capability of the stationary phase during RP-HPLC to induce secondary structure in long-chain linear peptides. Double D-amino acid replacement studies demonstrate that nonamphipathic helical domains can be recognized, even in the presence of highly amphipathic domains. On the other hand, systematic alteration of hydrophobicity at each residue along the sequence by methionine and methionine sulfoxide replacements results in characteristic pattern of HPLC retention-time differences, which is shown to provide a useful method to probe hydrophobic surface regions in helical peptides. Both amino acid replacement strategies were successfully applied to characterize the hydrophobically induced structure of oCRH. Although an alpha-helix is formed from residues 6 to 32, the N-terminal residues 1-5 and the C-terminal region 33-41 do not show any regular structure. The helical domain from residues 12 to 20 is highly amphipathic.

Amino Acid Sequence↗

PubMed1996

Corticotropin-releasing hormone (CRH) receptors in the mesenteric small arteries of rats resemble the (2)-subtype.

The potencies of the corticotropin-releasing hormone (CRH) agonistic peptides oCRH, h/rCRH, frog sauvagine, and carp urotensin I and of the antagonistic peptide alpha-helical CRH9-41 were compared in 3 different in vitro assays: (a) receptor binding to rat brain membranes; (b) release of ACTH/beta-endorphin from rat pituitary cells; and (c) relaxation of rat mesenteric small arteries. From their potency profiles, especially from the high potency of sauvagine relative to CRH in the relaxation assay, it is concluded that the receptors mediating the hypotensive action of systemic CRH in vascular smooth muscle are different from those in the pituitary and brain, and may be identical or very similar to the recently cloned new CRH receptor type 2.

Adrenocorticotropic Hormone↗

PubMed1996

Peptide helicity and membrane surface charge modulate the balance of electrostatic and hydrophobic interactions with lipid bilayers and biological membranes.

An amphipathic model peptide, KLALKLALKALKAAKLA-NH2, and its complete double D-amino acid replacement set was used to analyze the process of peptide binding at lipid vesicles of different surface charge and to determine the structure of the lipid-bound peptides using CD spectroscopy. The relationship between peptide helicity, model membrane permeability, and biological activity has been studied by dye release from liposomes and investigation of antibacterial and hemolytic activity. The accumulation of cationic KLAL peptides at and the membrane-disturbing effect on bilayers of high negative surface charge were found to be dominated by charge interactions. Independent of any structural propensity, the cationic peptide side chains bind to the anionic phosphatidylglycerol moieties. The charge interactions hold the peptides at the bilayer surface, where they may disturb preferentially lipid headgroup organization by formation of peptide-lipid clusters. In contrast, KLAL peptide interaction with bilayers of low negative surface charge is highly dependent on peptide helicity. With decreasing amounts of anionic phosphatidylglycerol in the bilayer the membrane-disturbing effect of KLAL and other helical analogs substantially increases despite drastically reduced binding affinity. Less helical peptides exhibit reduced bilayer-disturbing activity, showing that the hydrophobic helix domain is decisive for binding at and inducing permeability in membranes of low negative surface charge. It is suggested that hydrophobic interactions drive the penetration of the amphipathic peptide structure into the inner membrane region, thus disturbing the arrangement of the lipid acyl chains and causing local disruption. On the basis of the proposed model for membrane disturbance, interactions modulating antibacterial and hemolytic activity are discussed.

Amino Acid Sequence↗

PubMed1996

Conformational and functional study of magainin 2 in model membrane environments using the new approach of systematic double-D-amino acid replacement.

Systematic double-D-amino acid replacement of adjacent amino acids has been used to study the secondary structure of the amphiphilic, antibiotic peptide magainin 2 amide (M2a) by circular dichroism spectroscopy. Bound to liposomes, the secondary structure of the peptide is characterized by a weak alpha-helix in the N-terminus and a stable alpha-helix between residues 9 and 21. The lack of conformational differences in the peptide when bound to vesicles of varying negative charge density indicates marked independence of the structure from electrostatic forces. The similarity of the helicity profiles observed for double D-isomers bound to vesicles and in the presence of sodium dodecyl sulfate micelles (SDS) clearly shows that SDS can mimic magainin-lipid interactions. In contrast, in 1:1 trifluoroethanol/buffer (v/v), the peptide exhibits a weak alpha-helix extended from the N- to the C-terminus. Dye release experiments from vesicles of phosphatidylglycerol showed that double-D-amino acid substitution only in the region of the stable helix results in a reduction of the membrane-permeabilizing ability. On vesicles with a reduced amount of acidic phospholipids, double-D-amino acid substitution in any position leads to a drastic reduction of peptide-induced membrane permeabilization. Whereas the activity of M2a on phosphatidylglycerol was found to be mainly electrostatically determined, hydrophobic interactions play a decisive role in the interaction with vesicles of reduced negative charge density. Fluorescence investigations of tryptophan-containing analogs of high and low helicity showed that differences in the location of the chromophores of the membrane-bound peptides do not exist.

Amides↗

PubMed1996

A single-point slight alteration set as a tool for structure-activity relationship studies of ovine corticotropin releasing factor.

In order to determine which amino acid side chains of ovine corticotropin releasing factor (oCRF) are most sensitive to alterations with respect to receptor binding and activation, we synthesized a single-point replacement set by replacing each residue by a similar, preferably proteinogenic amino acid, maintaining a minimal change of character at each position (Ser by Thr, Gln by Asn, Glu by Asp, Arg by Lys, and vice versa, Pro by N-MeAla, Ile by Leu, Leu by Nle, Phe by Trp, His by Ala, Val by Leu, Met by Nle, Ala by Leu). In general, any loss in the biological potency by a single-point substitution in oCRF parallels a decrease in receptor binding, indicating that, in contrast to previous suggestions, there is no specific side chain in the peptide that is more responsible for receptor activation than for receptor binding. In addition to Arg(16), Ala(31), and Arg(35), amino acid residues in the N-terminal sequence (5-14) were found to be sensitive to alteration, demonstrating their particular importance for the receptor interaction of CRF agonists. Most of the analogs tested exhibited agonistic potencies in an in vitro pituitary cell culture assay at a concentration of 0.3 nM, and all analogs showed full agonistic potency at 1 microM. In contrast to the results of an alanine replacement study, the strongest decrease in receptor binding and biological potency was observed for analogs with substitutions of hydrophilic amino acids Ser(7), Arg(16), Glu(17), or Asn(34). In the case of Ser(7) and Arg(16), side chain specific interactions with the receptor may be required for high affinity. Alanine replacements at positions 17 or 34 resulted in analogs that were as potent as oCRF, while replacement of Glu(17) by Asp or Asn(34) by Gln caused a dramatic loss in potency, thereby suggesting an important effect at sterically or conformationally sensitive positions. In contrast to corresponding alanine analogs which exhibited a significant loss in biological potency, slight alterations of lipophilic side chains at positions 6, 12, or 38 did not cause a significant reduction of receptor binding and activation, indicating that it is not specific side chains but rather lipophilicity which is essential at these positions. Indeed, replacement of Phe(12) by Trp provides an agonist with significantly increased receptor binding and biological potency.

Adrenocorticotropic Hormone↗

PubMed1996

Distinct molecular recognition of calmodulin-binding sites in the neuronal and macrophage nitric oxide synthases: a surface plasmon resonance study.

The neuronal nitric oxide synthase and the macrophage nitric oxide synthase are differently regulated by Ca2+/calmodulin. We investigated the dynamics of calmodulin binding to the putative calmodulin-binding sites in both nitric oxide synthases. Peptides derived from the putative calmodulin-binding sites were synthesized and immobilized to a dextran layer of a biosensor chip. Complex formation of calmodulin and the peptides was monitored by surface plasmon resonance spectroscopy and recorded as sensorgrams. We determined a dissociation constant KD of 5.0 x 10(-9) M for the neuronal nitric oxide synthase and calmodulin. The association rate constant and the dissociation rate constant were ka = 1.58 x 10(5) M-1 s-1 and kd = 7.87 x 10(-4) s-1, respectively. Sensorgrams obtained with the macrophage nitric oxide synthase peptide were remarkably different. Calmodulin, once bound to the peptide, did not dissociate. Association of calmodulin to the peptide occurred with the same rate constants (ka = 3 x 10(4) M-1 s-1) regardless of the presence or absence of Ca2+. The affinity was in the subnanomolar range (KD) < 0.1 x 10(-9) M). We conclude that the extremely tight binding of calmodulin to the NOS-II is solely controlled by the calmodulin-binding segment and not by other parts of the protein.

Animals↗

PubMed1996

Ligand binding and functional effects of systematic double D-amino acid residue substituted neuropeptide Y analogs on Y1 and Y2 receptor types.

In order to identify the signal epitopes of the neuropeptide Y (NPY) molecule, the conformation of the NPY molecule was pertubated by a systematic double D-amino acid replacement of neighbouring residues. These NPY-analogs were examined for receptor affinity and on biological activity. The rat cerebral cortex and hippocampus were used for binding characteristics on Y1 and Y2 binding sites, respectively, while the isolated guinea pig caval vein and rat vas deferens were used in functional characterization of Y1 and Y2 receptors, respectively. The NPY analogs were examined as ligands at [3H]NPY binding sites in homogenates of the rat brain. Pairwise D-substitutions of either of the first 6 amino acid residues in the N-terminal part of the molecule resulted in a 20-100-fold loss of affinity for Y1 binding sites compared with the native peptide. In comparison, the same analogs displayed affinities, which were about 8-40 times lower than NPY itself at Y2 binding sites. Especially [D-Ser3,D-Lys4]NPY had a low affinity to Y1 and Y2 binding sites. For many of the pairwise D-amino acid substituted NPY analogs, there were similar affinities for Y1 and Y2 binding sites in the cerebral cortex and hippocampus, respectively. D-Amino acid residue substitutions in positions 7 and 8 did essentially not affect the affinity to either type of binding site, while such replacements in positions 19 and 20 resulted in a drastic loss of affinity to both types of NPY binding site. In contrast, [D-Tyr21,D-Ser22]NPY was only slightly less potent than NPY itself on either type of binding site. Pairwise D-amino acid substitutions in the C-terminal (positions 27 to 36) decreased the affinity to Y1 and Y2 binding sites by 2 to 3 orders of magnitude. In the guinea pig vena cava the D-amino acid substituted NPY analogs evoked a concentration-dependent contraction with an rank order of potency similar to that of the respective analog at Y1 binding sites in the cerebral cortex. Similarly, in the rat vas deferens the D-amino acid substituted NPY analogs evoked a concentration-dependent inhibition of the electrically-stimulated twitches with a rank order of potency similar to that of the respective analog at Y2 binding sites in the hippocampus. However, D-amino acid replacements in positions 25 and 26 resulted in an analog which was virtually inactive in the vas deferens, but almost equipotent with NPY in the vena cava. In conclusion, the present study has shown that N-terminal double D-amino acid substitutions in the NPY molecule reduced the binding affinity to and activation more of the Y1 receptor, than of the Y2 receptor, while both receptors were quite sensitive to double D-amino acid changes in positions 19 and 20 and in the C-terminal end of the NPY molecule.

Amino Acids↗

PubMed1996

Assignment of the helical structure in neuropeptide Y by HPLC studies of methionine replacement analogues and 1H-NMR spectroscopy.

The HPLC retention behavior of three complete single methionine and methionine sulfoxide replacement sets of two 18-mer model peptides and neuropeptide Y (NPY) were investigated. All peptides were prepared by multiple solid-phase peptide synthesis. Plotting the retention time differences between methionine and methionine sulfoxide analogues vs the position of replacement shows that potentially alpha-helical peptides become helical on binding during reversed-phase high performance liquid chromatography. In the case of an amphipathic alpha-helix, the retention time differences change periodically with a 3-4 repeat pattern, which allow the location of amphipathic helical structures. Replacements in nonamphipathic alpha-helical domains cause local preferential binding areas and lead to sequence-dependent retention time profiles. Methionine replacement studies of NPY suggest an unstructured or extended conformation from Tyr1 to Ala12 connected to a well-defined amphipathic alpha-helix from Pro13 to Arg35. The assignment is confirmed by comparison of nuclear Overhauser effects based two-dimensional 1H-nmr spectroscopy and utilization of the C alpha H shift index method in 50% trifluoroethanol/50% water.

Amino Acid Sequence↗

PubMed1996

Temperature coefficients of amide proton NMR resonance frequencies in trifluoroethanol: a monitor of intramolecular hydrogen bonds in helical peptides.

2D 1H NMR spectroscopy of two alpha-helical peptides which differ in their amphipathicity has been used to investigate the relationships between amide-proton chemical shifts, amide-proton exchange rates, temperature, and trifluoroethanol (TFE) concentration. In 50% TFE, in which the peptides are maximally helical, the amide-proton chemical shift and temperature coefficient patterns are very similar to each other in each peptide. Temperature coefficients from -10 to -6 ppb/K, usually indicative of the lack of intramolecular hydrogen bonds, were observed even for hydrophobic amino acids in the center of the alpha-helices. However, slow hydrogen isotope exchange for residues from 4 to 16 in both 18-mer helices indicates intact intramolecular hydrogen bonds over most of the length of these peptides. Based on these anomalous observations, we suggest that the pattern of amide-proton shifts in alpha-helices in H20/TFE solvents is dominated by bifurcated intermolecular hydrogen-bond formation between the backbone carbonyl groups and TFE. The amide-proton chemical shift changes with increasing temperature may be interpreted by a disruption of intermolecular hydrogen bonds between carbonyl groups and the TFE in TFE/water rather than by the length of intramolecular hydrogen bonds in alpha-helices.

Hydrogen↗

PubMed1996

Conformation of a water-soluble beta-sheet model peptide. A circular dichroism and Fourier-transform infrared spectroscopic study of double D-amino acid replacements.

Among peptide secondary structures beta-sheet domains have been much less intensively studied than alpha-helical conformations, mainly because of the lack of well characterized model peptides. In the present paper the secondary structure of a water-soluble de novo peptide consisting of 26 amino acids (DPKGDPKGVTVTVTVTVTGKGDPKPD-NH2) and the corresponding double D-amino acid replacement set have been studied by circular dichroism and Fourier-transform infrared spectroscopy. The model peptide was found to be unstructured in aqueous solution at peptide concentrations < 10(-3) mol/L but to adopt a predominantly beta-sheet structure in the presence of 15 mM sodium dodecyl sulfate or at apolar/water interfaces. Although the peptide is composed of amino acids with low helical propensity, it formed a single-stranded helical structure in aqueous trifluoroethanol. The D-amino acid replacement set was synthesized in order to study the conformational stability of the model peptide selectively in distinct regions. The data show that both the alpha-helix present in 50% trifluoroethanol as well as the beta-sheet domain formed in the presence of sodium dodecyl sulfate or at apolar/water interfaces, are located in the region between Val9 and Thr18. Pairwise substitution of adjacent amino acids by their corresponding D-amino acids provides a pronounced beta-sheet disturbance. These findings demonstrate that double D-amino acid replacements may be used to locate beta-sheet domains in peptides.

Amino Acid Sequence↗

PubMed1996

Conformational differences of ovine and human corticotropin releasing hormone. A CD, IR, NMR and dynamic light scattering study.

The differences in the conformational properties of ovine (o) and human (h) CRH in aqueous solution, structure-inducing TFE and in the presence of detergent micelles and lipid vesicles have been investigated by circular dichroism, Fourier transform infrared spectroscopy, NMR and dynamic light scattering. o-CRH was found to exist as a monomer with little regular structure in dilute aqueous solution. Association at concentrations higher than 10-3 mol/L results predominantly in dimers. The induction of a substantial amount of intermolecular beta-structure seems to be the result of interactions of the C-terminal hexapeptide and the N-terminal region 6-12 of o-CRH chains in antiparallel orientation. In contrast, h-CRH exhibits a high tendency of association which is highly sensitive to the pH. The formation of tetramers at millimolar peptide concentration is related to a helical content of ca. 50%. The potentially helical, highly hydrophobic region 6-20 enlarged by more hydrophobic residues in position 23 and 25 is proposed to stabilize the h-CRH associates. In the presence of structure inducing TFE (> 40% v) both CRH peptides exist as monomers. o-CRH reveals about 72% helicity, in h-CRH the formation of about 85% helix is observed. The differences in helicity of the two CRH molecules are located in the C-terminal heptapeptide, as concluded on the basis of NMR studies. Both peptides bind to detergent micelles at pH 4 as well as 7.4 associated with an increase in the alpha-helical content. Interaction of the two peptides with DMPC vesicles was found exclusively at pH 4. Above the phase transition temperature of DMPC the alpha-helical content in h-CRH increases slightly; however, o-CRH reveals a substantial amount of beta-type structure. The intramolecular type of beta-structure is associated with a deeper insertion of the o-CRH region 6-12 into the hydrophobic region of the lipid bilayer, whereas the corresponding region of h-CRH is kept in the bilayer surface. The higher helicity of h-CRH might explain to some extent its higher affinity to the CRH receptor, CRH antibodies and the CRH binding protein.

Animals↗

PubMed1996

Structure activity studies of mast cell activation and hypotension induced by neuropeptide Y (NPY), centrally truncated and C-terminal NPY analogues.

1. Neuropeptide-induced histamine release is thought to occur via receptor-independent mechanisms, with net charge and lipophilicity being important factors. 2. In this study, the histamine releasing ability of neuropeptide Y (NPY), two C-terminal segments of NPY and 13 centrally truncated NPY analogues was examined. These results were compared with the ability of the peptides to bind to the Y2 receptor in the rabbit kidney membrane model and with their hypotensive actions in the anaesthetized-rat model. 3. All analogues tested, with the exception of [Glu4,25,33,35]-NPY(1-4)-Ahx-(25-36) and [Asp4,25,33,35]NPY(1-4)-Ahx-(25-36) which were devoid of histamine releasing activity, evoked a dose-dependent histamine release but there were marked differences between the peptides. The native peptide was the least active. 4. Histamine release was not linked to the ability of the peptides to displace NPY from Y2 receptors. There was a statistical correlation between the hypotensive effects expressed as ED10 values (mumol kg-1, which induced a blood pressure decrease of 10 mmHg) and the EC25 for histamine release (r = 0.62, P = 0.04), although histamine release may not be the sole determinant of the alterations in blood pressure. 5. There was a strong negative correlation between EC25 for histamine release and net positive charge (r = -0.93, P = 5.7 x 10(-7), i.e. increasing the net positive charge caused greater histamine release. However, there was a 12 fold difference in activity amongst the most positively charged analogues (+5). Helicity did not correlate with histamine releasing ability. 6. In the development of NPY-related drugs the avoidance of compounds with net positive charge is recommended.

Animals↗

PubMed1995

Influence of alpha-helicity, amphipathicity and D-amino acid incorporation on the peptide-induced mast cell activation.

Mast cell activation by polycationic substances is believed to result from a direct activation of G protein alpha subunits and it was suggested that the adaption of amphipathic, alpha-helical conformations would allow the peptide to reach the cytosolic compartment to interact with G proteins (Mousli et al., 194, Immunopharmacology 27, 1, for review). We investigated the histamine-releasing activity of model peptides as well as analogues of magainin 2 amide and neuropeptide Y with different amphipathicities and alpha-helix content on rat peritoneal mast cells. Amphipathic helicity is not a prerequisite for mast cell activation. Moreover, non-helical magainin peptides with high histamine-releasing activity were less active in the liberation of carboxyfluoresceine from negatively charged liposomes, indicating that peptide-induced mast cell activation and peptide-induced membrane perturbation do not correlate. In contrast to the negligible influence of the secondary structure, amino acid configuration may exert a striking influence on peptide-induced mast cell activation. Thus histamine-release by substance P was markedly impaired when the L-amino acids in the positively charged N-terminal region were replaced by D-amino acids, with [D-Arg1)substance P being the most inactive substance P diastreoisomer.

Amino Acid Sequence↗

PubMed1995

Structure effects of double D-amino acid replacements: a nuclear magnetic resonance and circular dichroism study using amphipathic model helices.

D-Amino acid replacements and the determination of resulting structural changes are a useful tool to recognize amphipathic helices in biologically active peptides such as neuropeptide Y and corticotropin-releasing factor. In this paper the secondary structures of one amphipathic alpha-helical peptide and its double D-amino acid analog have been determined by means of 1H NMR and CD spectroscopies under equivalent conditions. The chemical shifts (NH and C alpha H) and the analysis of nuclear Overhauser effects show a split of the continuous helix for the all-L peptide into two helices at the position of double D-amino acid replacement. Hydrogen exchange rates correlate with water accessibilities in the hydrophobic/hydrophilic face and confirm the amphipathic helical structure in the all-L peptide as well as in its double D-amino acid analog. A significantly accelerated hydrogen isotope exchange rate is observed for the D-Ala9 backbone proton, implying an increased flexibility at that position. These results show that the incorporation of an adjacent pair of D-amino acids only causes a local change in structure and flexibility, which makes the double D replacement interesting as a tool for specific helix-disturbing modifications to search for helical conformations in biologically active peptides.

Amino Acid Sequence↗

PubMed1995

Location of an amphipathic alpha-helix in peptides using reversed-phase HPLC retention behavior of D-amino acid analogs.

The reversed-phase HPLC retention behavior of D-amino acid replacement sets of an amphipathic model peptide, neuropeptide Y, and corticotropin releasing factor has been studied. The results demonstrate that D-amino acid substitutions destabilized the amphipathic alpha-helix, leading to a decrease of fractional helicity as determined by circular dichroism. The effect is enhanced by substitution of two adjacent D-amino acids and correlates well with a decrease of hydrophobic interaction during reversed-phase HPLC, caused by disturbance of the preferred binding domain of the stationary phase-bound peptide. In contrast, D-amino acid substitutions in nonamphipathic or disordered regions of peptides do not influence the retention time to the same extent. Thus, the "retention profile" that results from plotting the retention time vs the position of the double D-amino acid replacements provides an indication of the presence and location of an amphipathic alpha-helical secondary structure in peptides.

Amino Acid Sequence↗

PubMed1995

Recognition of alpha-helical peptide structures using high-performance liquid chromatographic retention data for D-amino acid analogues: influence of peptide amphipathicity and of stationary phase hydrophobicity.

The reversed-phase HPLC behaviour of double D-amino acid replacement sets of amphipathic and non-amphipathic helix-forming peptides consisting exclusively of leucine, lysine and alanine residues was studied on different polymer-encapsulated silica-based stationary phases. Plotting the retention times versus the position of D-amino acid substitution gives a characteristic pattern showing decreased retention times in the helical region. The retention time profile obtained using an amphipathic alpha-helix is caused by disturbance of the preferred binding domain of the stationary phase-bound peptide. However, the effect is similar but less pronounced using a non-amphipathic helical peptide that is unable to interact by a preferred binding site. The results demonstrate that reversed-phase HPLC data for peptide analogues provide an indication event of a non-amphipathic helical structure in peptides.

Amino Acid Sequence↗

PubMed1995

MALDI-MS for C-terminal sequence determination of peptides and proteins degraded by carboxypeptidase Y and P.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used for C-terminal amino acid sequence determination of peptides and proteins. The usefulness of MALDI-MS was demonstrated by analyzing peptide mixtures (C-terminal peptide ladder) which were generated by enzymatic digestion of substance P, glucagon, angiotensinogen, insulin B chain and myoglobin with the exopeptidases carboxypeptidase Y and P. The results clearly show that up to 11 amino acid residues can be determined in the pmol range by analyzing the molecular masses of the truncated peptides. For proteins it is possible to investigate enzymatic or chemical digests in the same manner.

Amino Acid Sequence↗

PubMed1994

Determination of peptide hydrophobicity parameters by reversed-phase high-performance liquid chromatography.

The log kw values of fourteen potential fibrinogen receptor antagonist peptides (RGDX) determined by reversed-phase HPLC were correlated to hydrophobic parameters of the amino acid side-chain log P in position X of the tetrapeptides. Comparing the polymer columns with LiChrosorb RP-8, the correlation coefficient using a polyethylene column is higher (0.94) than that for RP-8 (0.88), which demonstrates the importance of a homogeneous hydrophobic surface and makes this method very suitable for the determination of the overall hydrophobicity of shorter peptides. The hydrophobicity parameters log kw of the RGDX peptides (-1.15 to 2.19) were used to investigate the influence of molecular parameters of X on the potency of RGDX in inhibiting platelet aggregation. The results confirm the importance of hydrophobicity for the contribution of X to the biological activity of RGDX.

Amino Acid Sequence↗