1,721,045 research outputs found
Synthesis and biological activity of D-glucopyranosyl peptide T derivatives
No full textThe solid phase procedure, based on the Fmoc (9-fluorenylmethyloxycarbonyl) chemistry, was used to prepare some peptide T analogues in which D-glucopyranosyl units are beta-O-glycosidically linked to Thr4 and/or Thr5 side chains. All glycopeptides showed significant human monocyte chemotaxis and high resistance to degradation by plasma or brain enzymes
Synthesis and biological activity of chelator-peptide T conjugates
No full textThe solid phase procedure was used to prepare two peptide T derivatives in which the 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoyl unit is linked to their N-terminus. In a human monocyte chemotaxis assay, both chelator-peptide conjugates showed a high binding property to the CD4 receptor, comparable to the parent H-D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH2 and its pentapeptide fragment T(4-8)-NH2. These encouraging results make the above cyclam-oligopeptides candidates for the development of the CD4 receptor imaging agents
Opioid peptides: Structure-activity relationships of dermorphin endothiotetrapeptides. VII
No full textWe describe the synthesis and preliminary in vitro and in vivo pharmacological tests of five endothiotetrapeptide analogues of the opioid heptapeptide dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser.-NH2. The modification obtained by substituting Phet for Phe3 or Glyt for Gly4 provided further analogues with significant opioid activity
Synthesis and activity of dermorphin-growth hormone releasing factor hybrid peptides
No full textDermorphin- growth hormone releasing factor (GRF) hybrid peptides (Y-Tyr-D-Ala-Xaa-Gly-Tyr-Pro-Ser-NH2) were synthesized and tested for opioid activity and their ability to stimulate growth hormone (GH) secretion. The substitution of Phe3 for Asp and Glu in dermorphin or its N-terminal acetylation produced peptides with no affinity for opioid receptors but significant, even if low, GRF-like activity
Reversed-phase HPLC study on the in vitro enzymic degradation of dermorphin
No full textA high-performance liquid chromatographic (HPLC) method for the separation of the opioid heptapeptide dermorphin and related fragments has been developed. The chromatographic system was applied in the study of the kinetics of degradation of dermorphin (Der) in various tissues. Der was found to be extremely resistant to human and rat plasma (T 1/2 greater than 180 min). Upon incubation with homogenates of rat brains and kidneys, Der was cleaved with a half-life of 20.8 +/- 2.2 min and 2.4 +/- 0.3 min respectively. The catabolite formed was identified, in both tissues, as the N-terminal tetrapeptide H-Tyr-D-Ala-Phe-Gly-OH. The stability to rat kidney and brain of the N-terminal hexa- and pentapeptides and of the [4 psi 5, NHCO] Der analogue was also investigated. The nature of the enzyme systems involved in the in vitro degradations is discussed
Opioid peptides. Synthesis and binding assays of desamino-Tyr1 dermorphin analogues. XII
No full textEight new dermorphin peptides, X-C6H4-CH2CH2CO-D-Ala-Phe-(L or D)-Yaa-NH2 [X = H, OH; Y = lysine, homoarginine (Har)], were prepared and tested by binding assays. They show negligible affinity for mu-, delta- and K-receptor sites. These findings indicate that the N-terminal ammonium group can not be replaced by the ammonium or guanidinium function located at the side-chain in Lys or Har derivatives
Synthesis and pharmacological activity of the N‐terminal dermorphin tetrapeptide analogs with CH2‐NH peptide bond isosteres
No full textThe synthesis of pseudotetrapeptides H-Tyr-D-Ala-Phe-NH-(CH2)2--NH2 (1a), H-Tyr-D-Ala-Phe-psi (CH2--NH)-Gly-NH2 (2a), H-Tyr-D-Ala-psi (CH2--NH)-Phe-Gly-NH2 (3a), and H-Tyr-psi (CH2--NH)-D-Ala-Phe-Gly-NH2 (4a), representing the N-terminal tetrapeptide sequence of dermorphin, in which amide bonds are replaced by CH2--NH bond, is described. N-acetyl-Tyr and desamino-Tyr pseudopeptide analogs (1-4b), (1-3c) are also described. The analogs were assayed in binding studies based on displacement of mu and delta-receptor selective radiolabels from rat brain membrane and in a bioassay using guinea pig ileum (GPI). Pseudopeptides in which the C-terminal (1a) or D-Ala-Phe (3a) amide bond are substituted, exhibit higher mu-affinities and mu-receptor selectivity than the corresponding Phe-Gly or Tyr-D-Ala analogs (2a, 4a). Acetyl-and desamino-Tyr pseudopeptide analogs (1-4b) and (1-3c) did not exhibit mu and delta-opioid receptor affinity at nM concentration. The relevance of the single peptide replacement and of its association to acetylation or amino group elimination of Tyr, is discussed on the basis of a receptor model for mu and delta opioids
Opioid peptides. Synthesis and biological properties of dermorphin related hexapeptides
No full textThe Gly 4 and/or Tyr 5 residues in dermorphin hexapeptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-OH) were replaced by Nα-methyl- or D-amino acids in order to examine the effect on opioid activity. Two pseudopeptides (H-Tyr-D-Ala-Phe-Gly-ψ (NHCO)-Xaa-Pro-OH, Xaa - Tyr or Phe) in which the Gly 4-Xaa bond is reversed, were also prepared. Metabolic stability, analgesia and selectivity of these compounds for different receptor populations have been investigated. Results suggest that the 12 new analogues showed a negligible affinity for the K binding site and some selectivity for μ- or δ receptors. In some cases the analgesic potencies seems to be related to enzymatic stability of the peptides
Synthesis and opioid activity of dermorphin tetrapeptides beearing D-methionine S-oxide at position 2
No full textEight new dermorphin tetrapeptides, X-Tyr-D-MetO-Phe-aa-Y (X = H, H2N = C(NH); aa = Gly, 2-aminoethanol, sarcosine; Y = NH2, NH-alkyl), were prepared and tested for opioid activity. They show dose-related naloxone-reversible opioid effects in vitro and in vivo. H-Tyr-D-MetO-Phe-Gly-NH2 (I) (guinea pig ileum IC50 = 13.6 nM; tail-flick ED50 = 1.97 pmol/mouse, icv, and 0.65 mumol/kg, sc), though less effective in the periphery, has central activities higher than those of dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2. Following intracerebroventricular or subcutaneous administrations in mice, I is about respectively 1500 and 17 times as potent an analgesic as morphine
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