PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Bioactive peptide”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2002

Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR.

In order to clarify the potential physiological function of royal jelly (RJ), we report here the gastrointestinal enzyme production of antihypertensive peptides from RJ. Intact RJ and its protein fraction did not retard the action of angiotensin I-converting enzyme (ACE) activity at all. However, development of ACE inhibition power of RJ was newly observed by pepsin hydrolysis (IC(50)=0.358 mg protein/mL), and the subsequent trypsin and chymotrypsin hydrolyses (IC(50)=0.099 mg protein/mL). Single oral administration of this gastrointestinal RJ hydrolysate (1 g/kg dose) in 10-week spontaneously hypertensive rat resulted in a significant reduction of systolic blood pressure of 22.7 plus minus 3.6 mmHg at 2 hr (P<0.05 vs. 0 hr by one-way ANOVA, n=7). Then, the RJ hydrolysate was fractionated with gel permeation chromatography to obtain the di- and tri-peptides (DTP) fraction. As a result of isolation from the DTP fraction by reversed phase-high performance liquid chromatography, eleven ACE inhibitory peptides were isolated from the DTP-RJ hydrolysate. Some of the ACE inhibitors were derived from the RJ-glycoprotein; eight peptides with the IC(50) value of <10 &mgr;M were identified from natural resources for the first time. Consequently, RJ protein was thought to be a good resource of ACE inhibitory peptides produced by the gastrointestinal enzyme hydrolyses.

Journal Article↗
PubMed2002

A novel route to radioiodinated [123I]-N-succinimidyl-3-iodobenzoate, a reagent for radioiodination of bioactive peptides.

Radiolabeled peptides continue to emerge as potential radiopharmaceuticals for targeting several diseases such as cancer, infection and inflammation and even tissue and organ rejection. The classical method for labeling these molecules has been the electrophilic route. Evidence suggests that most molecules labeled via this route perturb their biological activity. Moreover, this method is not applicable to peptides lacking a tyrosine moiety in their structure. Hence, there is the need to develop alternate methods such as the prosthetic approach. We have optimized a solid-state radioiodination by exchange to produce [123I]-metaiodobenzylguanidine ([123I]-mIBG). The mIBG served as a precursor to obtain an activated N-succinimidyl ester for efficient coupling to amine functions in peptides, preferably the lysine group(s). The method was used to label a model chemotactic peptide and evaluated in vivo.

Animals↗
PubMedDate not supplied

Rigid linkers for bioactive peptides.

Rigid linkers of variable length were used to connect two high-affinity Nle4-D-Phe7-alpha-melanocyte stimulating hormone (NDP-alpha-MSH) or two low-affinity MSH(4) ligands. The linked peptides were synthesized by solid-phase methods. Control experiments indicate there is little or no effect of these linkers on NDP-alpha-MSH or MSH(4) binding to the human melanocortin 4 receptor (hMC4R). Tethering two high-affinity ligands gave no binding enhancement, while tethering two low-affinity ligands resulted in binding enhancement that decreased with increased linker length. Furthermore, for the low-affinity ligands, the enhancement of affinity is inversely proportional to the estimated molecular moments of inertia. These results are consistent with a model wherein binding is enhanced when the rate of ligand reattachment to the receptor is fast relative to the rate of ligand diffusion.

Cell Line↗
PubMed2004

Distributed computing and NMR constraint-based high-resolution structure determination: applied for bioactive Peptide endothelin-1 to determine C-terminal folding.

Distributed computing has been implemented to the solution structure determination of endothelin-1 to evaluate efficiency of the method for NMR constraint-based structure calculations. A key target of the investigation was determination of the C-terminal folding of the peptide, which had been dispersed in previous studies of NMR, despite its pharmacological significances. With use of tens of thousands of random initial structures to explore the conformational space comprehensively, we determined high-resolution structures with good convergences of C-terminal as well as previously defined N-terminal structures. The previous studies had missed the C-terminal convergence because of initial structure dependencies trapped in localized folding of the N-terminal region, which are strongly constricted by two disulfide bonds.

Endothelin-1↗
PubMed2003

Bioactive peptidic analogues and cyclostereoisomers of the minimal antinociceptive histogranin fragment-(7-10).

Novel analogues of the minimal antinociceptive histogranin (HN) fragment Gly(7)-Gln-Gly-Arg(10), in which amino acids in positions 8, 9, and 10 were replaced by lipophilic amino acids and corresponding d-amino acid residues in combination with N- to C-terminal cyclization, were synthesized and tested in various animal models of pain. All synthetic compounds were potent and efficacious analgesics in the mouse writhing test. Cyclic [-Gly-Ala-Tyr-d-Arg-] (9) and cyclic [-Gly p-Cl-Phe-Tyr-d-Arg-] (10) were the most potent analgesics, being 17 and 135 times as potent as HN, respectively (AD(50) of 1.37 and 0.17 nmol/mouse icv, as compared with 23 nmol/mouse for HN). The times of action of compounds 9 and 10 were also much improved with half-maximal effects still being observed 60 min and >90 min after their administration, respectively, as compared with 8.1 min for the parent peptide HN-(7-10) and 22.1 min for HN. At analgesic doses, compounds 9 and 10 were devoid of motor effect as assessed by the mouse rotarod assay. As already observed with HN, compounds 9 (10 nmol/rat; i.t.) and 10 (0.5 nmol/rat; i.t.) were effective in blocking persistent inflammatory pain in the formalin test and hyperalgesia induced by intraplantar administration of complete Freund adjuvant. In addition, the analgesic effects evoked by compounds 9 (10 nmol/mouse; icv) and 10 (1 micromol/kg; i.v.) in the mouse writhing test and compound 9 (10 nmol/mouse; icv) in the mouse tail flick assay were similarly antagonized by the dopamine D(2) receptor antagonist raclopride (1 nmol/mouse; icv) but not the opiate antagonist naloxone (1 nmol/mouse; i.c.v). Finally, the various cyclic compounds competed with the binding of [(3)H]raclopride in rat brain membrane preparations. Their ability to compete with the binding of the D(2) ligand correlated well with their potency in alleviating pain in the mouse writhing test (r = 0.95). These results indicate that the analgesic activity of the minimal active core in HN can be improved by changes that favor its interaction with the dopamine D(2) receptor.

Analgesics↗
PubMed1996

1-Aminocyclobutanecarboxylic acid derivatives as novel structural elements in bioactive peptides: application to tuftsin analogs.

Four novel 2,4-methano amino acids (MAAs, 1-aminocyclobutane-1-carboxylic acids) were synthesized. These include the basic MAA analogs of lysine (16), ornithine (5), and arginine (6) and the neutral methanovaline (22), related to proline. The above MAAs, as well as the MAA analog of homothreonine (7), were incorporated into the peptide chain of the immunomodulatory peptide tuftsin, Thr-Lys-Pro-Arg, known to enhance several biological activities mediated by phagocytic cells. The synthetic methano tuftsin analogs were assayed for their ability to stimulate interleukin-6 (IL-6) secretion by mouse peritoneal macrophages and for their stability in human serum toward enzymatic degradation. It was found that, at 2 x 10(-7) M, [MThr1]tuftsin (24) and an isomer of [MVal3]tuftsin (27a) were considerably more active than the parent peptide in augmentation of cytokine release. [MOrn2]Tuftsin (25) was equally potent. The analogs [MThr1]tuftsin (24) and [MOrn2]tuftsin (25), both pertaining to the proteolytically sensitive Thr-Lys bond of tuftsin, exhibited high resistance to enzymatic hydrolysis as compared to tuftsin. Using specific rabbit anti-tuftsin antibodies in a competitive enzyme-linked immunosorbent assay (ELISA) revealed that none of the MAA analogs can cross-react with tuftsin. It may indicate that the peptides assume global structures different than that of tuftsin.

Amino Acids↗
PubMed2004

Microcionamides A and B, bioactive peptides from the philippine sponge Clathria (Thalysias) abietina.

Microcionamides A (1) and B (2) have been isolated from the Philippine marine sponge Clathria (Thalysias) abietina. These new linear peptides are cyclized via a cystine moiety and have their C-terminus blocked by a 2-phenylethylenamine group. Their total structures, including absolute stereochemistry, were determined by a combination of spectral and chemical methods. Compound 1 was shown to slowly isomerize about the C-36/C-37 double bond when stored in DMSO. Microcionamides A (1) and B (2) exhibited significant cytotoxicity against the human breast tumor cells lines MCF-7 and SKBR-3 and displayed inhibitory activity against Mycobacterium tuberculosis H(37)Ra.

Animals↗
PubMed1990

Transdermal delivery of bioactive peptides: the effect of n-decylmethyl sulfoxide, pH, and inhibitors on enkephalin metabolism and transport.

We investigated the effects of the nonionic surfactant, n-decylmethyl sulfoxide (NDMS), pH, and inhibitors on the metabolism and the permeation of amino acids, dipeptides, and the pentapeptide enkephalin, through hairless mouse skin. An HPLC gradient method was developed to identify the possible peptide and amino acid metabolites of leucine-enkephalin. NDMS increased the permeability of all amino acids and peptides tested. At neural pH, the enzyme activity within the skin was such that no flux of leucine-enkephalin (YGGFL) was observed and the donor cell concentration of YGGFL decreased rapidly. The major cleavage occurred at the Tyr-Gly bond. At pH 5.0 the metabolic activity was reduced significantly and a substantial flux of YGGFL was observed. Enzymatically stable YGGFL analogues, Tyr-D-Ala-Gly-Phe-Leu (YDAGFL) and its amide, exhibited significant fluxes even at neutral pH in the presence of NDMS, but with substantial metabolism. YDAGFL amide was more stable to metabolism than YDAGFL. The rates of metabolism of the peptides in the skin homogenates were in the order: FL much greater than YGGFL greater than GFL greater than GGFL much greater than YG, YGG much greater than YDAGFL amide. In the skin homogenates puromycin and amastatin showed the highest inhibitory effects, while FL and GFL were only slightly active. However, in the skin diffusion experiments, FL allowed the highest amount of intact parent compound to permeate, making it the most potent inhibitor. These results show that the complex proteolytic enzyme activities occurring during skin permeation are different from those in skin homogenates and that a combination of enhancer, pH adjustment, and inhibitors can increase the transdermal delivery of peptides.

Administration, Cutaneous↗
PubMed2004

Bioactive peptides based on diversity libraries, supramolecular chemistry and rational design: a new class of peptide drugs. Introduction.

A new class of pharmaceutical molecules--synthetic vaccines, synthetic diagnostics and peptide drugs--are emerging based on recent advances of peptide libraries, supramolecular chemistry and rational design. The molecules of this growing class have exciting potential, not met by classical drugs based on small molecules or recombinant proteins.

Combinatorial Chemistry Techniques↗
PubMed1995

Interaction between pregnancy-induced bioactive peptides and the placental proteases.

Studies have shown that placental proteases metabolize vasoactive peptides, possibly derived from the fetus, and protect the exchange of peptide hormones across the placenta in order to maintain feto-placental homeostasis. Changes in maternal serum protease activities were useful for monitoring pre-eclampsia and predicting the onset of labour. The study showed that possible role of oxytocinase in the maintenance of gestation and the possible involvement of angiotensinase in the attenuated pressor responses to angiotensin II during pregnancy, respectively. In addition, the ratio of peak systolic over least diastolic pressure (S/D) of uterine or umbilical artery assessed by the Doppler technique was closely correlated with the concentrations of maternal serum proteases in pre-eclampsia, which suggested that placental proteases might control utero-placental circulation via the regulation of concentrations of vasoactive peptides in uteroplacental circulation.

Cystinyl Aminopeptidase↗
PubMed1991

Heterologous in vivo processing of human preproendothelin 1 into bioactive peptides.

Endothelin (ET) is an extremely potent vasoconstrictor peptide of 21 amino acids, originally found in the supernatant of cultured vascular endothelial cells. To gain insights into its biosynthetic pathway, we expressed a synthetic RNA coding for the 212-amino acid precursor of human ET-1 (preproET-1) in Xenopus oocytes. Cell homogenates and oocyte incubation medium were tested by RIA using an anti-ET-1 serum. ET-1-like immunoreactivity was detected in oocytes injected with preproET-1 synthetic RNA but not in control oocytes and was much higher in medium than in cell homogenates. When preproET-1 was expressed in oocytes treated with monensin, a dramatic decrease in secretion of immunoreactive material was observed, indicating that secretion is mediated by the Golgi complex. ET-1-like immunoreactive material present in oocyte incubation medium was fractionated by reverse-phase HPLC into two main peaks, corresponding to the retention times of human big ET-1 and ET-1. Incubation medium of oocytes expressing the synthetic preproET-1 RNA elicited a characteristic vasoconstrictor response on rabbit vena cava, consistent with the biological activity that would be predicted from the amount of ET-1-like immunoreactivity measured. These results suggest that common pathways of ET maturation exist in widely different cells and that Xenopus oocytes may represent a useful tool in studying the cell biology of ET-1 synthesis.

Animals↗