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Cyclic Analogues (cyclic + analogue)
Selected AbstractsSynthesis of a Cyclic Analogue of GalardinCHINESE JOURNAL OF CHEMISTRY, Issue 3 2001Da-Wei Ma Abstract A cyclic analogue 4 of galardin, a known MMP inhibitor, is designed to improve its selectivity. The synthesis of 4 starts from dimethyl (S)-malate using diaselective alkylation and subsequent cyclization and amide formation as key steps. The compound 4 showed MMP inhibitory activity on all MMPs tested with IC30, ranging from 20.1 ,M to 104 ,M. [source] Immunosuppressory activity of ubiquitin fragments containing retro-RGD sequenceBIOPOLYMERS, Issue 5 2004Zbigniew Szewczuk Abstract A peptide fragment corresponding to the ubiquitin50,59 sequence (LEDGRTLSDY) (U50,59) possesses a very high immunosuppressory activity, comparable to that of cyclosporine, both in the cellular and humoral immune responses. We found that the pentapeptide DGRTL (U52,56) is the shortest, effective immunosuppressory fragment of ubiquitin, although its potency is weaker than that of U50,59. Replacement of each consecutive residue with alanine in U52,56 allowed identification of essential amino acids involved in the immunosuppression. We also evaluated the roles of its N- and C-terminal groups by their acetylation and/or amidation, respectively. The active sequence is located in the external loop of the molecule and therefore it may serve as an important functional epitope for intermolecular binding. Based on the crystal structure of ubiquitin molecule, we designed and synthesized the cyclic analogue with a restricted conformation, cyclo(Glt,Gln,Leu,Glu,Asp,Gly,Arg,Thr,Leu,Ser,Asp,Lys),NH2 (Glt = glutaryl) by reacting the C-terminal Lys side chain with the glutarylated N-terminus. The peptide was designed to mimic the ubiquitin48,59 loop, in order to obtain the ligand that may interact with hypothetical receptors of the loop. The cyclization product selectively but strongly suppresses the cellular immune response. The results indicate that the 48,59 loop may serve as an important functional epitope in the ubiquitin molecule for intermolecular binding. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004 [source] Synthesis of a Cyclic Analogue of GalardinCHINESE JOURNAL OF CHEMISTRY, Issue 3 2001Da-Wei Ma Abstract A cyclic analogue 4 of galardin, a known MMP inhibitor, is designed to improve its selectivity. The synthesis of 4 starts from dimethyl (S)-malate using diaselective alkylation and subsequent cyclization and amide formation as key steps. The compound 4 showed MMP inhibitory activity on all MMPs tested with IC30, ranging from 20.1 ,M to 104 ,M. [source] Cyclopeptides of Linum usitatissimumJOURNAL OF PEPTIDE SCIENCE, Issue 9 2006Boles, aw Picur Abstract Cyclolinopeptide A (CLA), a cyclic nonapeptide from linseed, possesses strong immunosuppressive and antimalarial activity along with the ability to inhibit cholate uptake into hepatocytes. The structure of the peptide was studied extensively in solution as well as in the solid state. It is postulated that both the Pro,Pro cis -amide bond and an ,edge-to-face' interaction between the aromatic rings of two adjacent Phe residues are important for biological activity. Structure,activity relationship studies of many linear and cyclic analogues of CLA suggest that the Pro-Xxx-Phe sequence and the flexibility of the peptide are important for the immunosuppressive activity. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Structural characterization of cyclic kallidin analogues in DMSO by nuclear magnetic resonance and molecular dynamicsJOURNAL OF PEPTIDE SCIENCE, Issue 1 2005Elisabetta Schievano Abstract The conformational properties in DMSO of two head-to-tail cyclic analogues of kallidin ([Lys0]-bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr6]-KL (YKL), [Trp6]-KL (WKL), cyclo-([Tyr6]-KL) (YCKL) and cyclo-([Trp6]-KL) (WCKL). The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo-KL. The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X-Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X-Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X-Pro bond and always opposite configuration for the two consecutive X-Pro bonds. The NOE-restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthesis, conformation and biological activity of linear and cyclic Thr6 -bradykinin analogues containing N -benzylglycine in place of phenylalanine,JOURNAL OF PEPTIDE SCIENCE, Issue 12 2001L. Biondi Abstract Three linear Thr6 -bradykinin analogues in which either one or both the two phenylalanine residues in the peptide sequence have been substituted by N -benzylglycine (BzlGly) and their head-to-tail cyclic analogues were synthesized and tested on an isolated rat duodenum preparation. The linear (BzlGly5,Thr6 -BK, BzlGly8,Thr6 -BK and BzlGly5,8,Thr6 -BK) and the cyclic (cyclo BzlGly5,Thr6 -BK, cyclo BzlGly8,Thr6 -BK and cyclo BzlGly5,8,Thr6 -BK) peptoid-like analogues were characterized by amino acid analysis, optical rotation, analytical HPLC and MALDI-TOF mass spectroscopy. The conformational features of both the linear and cyclic derivatives were investigated by FT-IR and CD measurements. Preliminary molecular mechanics calculations were also performed on some synthetic peptides. Pharmacological screening using the relaxation of the isolated rat duodenum preparation showed that incorporation of N -benzylglycine at positions 5 and/or 8 in the linear Thr6 -BK causes a substantial decrease in potency. Comparable incorporation in cyclo Thr6 -BK, at position 8, or 5 and 8, resulted in nearly inactive analogues. However, cyclo BzlGly5,Thr6 -BK showed a potency which is of the same order of magnitude as for cyclo -BK and cyclo Thr6 -BK. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Solid-phase synthesis of cyclic analogues related to the hypoglycaemic peptide hGH[6,13]: Comparison of two i,i+4 lactam cyclization proceduresJOURNAL OF PEPTIDE SCIENCE, Issue 10 2001Vittoria Cavallaro Abstract The use of 1,3-diisopropylcarbodiimide (DIC) for the synthesis of cyclic analogues of the hypoglycaemic peptide fragment derived from the N -terminus of human growth hormone (hGH), namely hGH[6,13], is described. Different strategies were examined to achieve improved yields for the on resin side-chain to side-chain cyclization of the corresponding linear peptides containing reverse , - turn motifs. When compared with the more reactive Castro's reagent, the results confirm that DIC in the presence of HOBt can be successfully employed to minimize the formation of intermolecular oligomeric by-products associated with the preparation of cyclic hGH[6,14] peptide analogues based on an i,(i+4)Lys,Glu or Glu,Lys cyclization strategy. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] | ||||||||||