Synthesis and immunosuppressive activity of cyclolinopeptide A analogues containing homophenylalanine.

Immune response suppressors are used in the medical praxis to prevent graft rejection after organ transplantation and in the therapy of some autoimmune diseases. Cyclolinopeptide A, naturally existing immunomodulatory peptide, was modified with homophenylalanine in positions 3 (4), 4 (5) or both 3 and 4 (6). The conformational influence of the replacement of Phe by Hphe was analyzed by NMR spectroscopy.

Analogues of neurohypophyseal hormones, oxytocin and arginine vasopressin, conformationally restricted in the N-terminal part of the molecule.

It is generally accepted that the conformation of the N-terminal part of neurohypophyseal hormones analogues is important for their pharmacological activity. In this work, we decided to investigate how the substitution of positions 2 and 3 with the ethylene-bridged dipeptide would alter the pharmacological properties of OT, [Mpa1]OT, and [Cpa1]OT (OT=oxytocin; Mpa=3-mercaptopropionic acid; Cpa=1-mercaptocyclohexaneacetic acid) and to investigate how a bulky 3,3-diphenyl-L-alanine residue incorporated in position 2 of AVP, [Mpa1]AVP, and [Cpa1]AVP (AVP=arginine vasopressin) would change the pharmacological profile of the compounds. The next analogues, [Val4]AVP, [Mpa1,Val4]AVP, and [Cpa1,Val4]AVP, had N-benzyl-L-alanine introduced at position 3.

Chelating ability of proctolin tetrazole analogue.

The aim of the investigation was to establish the chelating ability of a new proctolin analogue of the sequence Arg-Tyr-LeuPsi[CN(4)]Ala-Thr towards copper(II) ions. The insertion of the tetrazole moiety into the peptide sequence has considerably changed the coordination ability of the ligand. Potentiometric and spectroscopic (UV-Vis, CD, EPR) results indicate that the incorporation of 1,5-disubstituted tetrazole ring favours the formation of a stable complex form of CuH(-1)L.