Alpha,Beta-Hybrides of opioid peptides analogues

• Autorzy: Olma A. , Podwysocka D. , Lipkowski A.W. , Kosson P.
• Języki publikacji: EN

Abstrakty

EN

Endogenous opioid peptides like enkephalins endomorphin, dermorphin and deltorphins are model peptides for the development of new analgesic drugs. Since the discovery of the endogenous opioid peptides, numerous analogues have been synthesized in attempts to develop an analgesic without the serious side effects. A major problem with opioid peptides as drugs is their susceptibility to enzymatic hydrolysis when administrated in vivo. Different chemical approaches, as the incorporation of D-amino acids, unnatural amino acid, α,α-disubstituted amino acids, cyclization, have resulted in more stable analogues. Among the numerous suggestions for modification the substitution of β-amino acids for proteinogenic amino acids represents an interesting possibility. ²-Peptides, oligomers of ²-amino acids are a very actual subject of research. β-Peptides do not bind to the active sites of human peptidases and they are entirely stable against proteolytic degradation. On the other hand β-peptides can mimic α-peptides. This was demonstrated that small β-peptides with their strong folding preferences may be used as pharmaceutically active compounds. In this communication we report the effect on receptor binding single replacements in β3 -hybrides of deltorphin I, µ-selective ligands, tetrapeptide Tyr-D-Ala-Phe-Phe-NH2 (TAPP) and biphaline. Nprotected β3 -homo-amino acids were synthesized using procedures reported in the literature. α-Amino acids are enantiomerically pure, commercially available compounds which have frequently used as starting materials for synthesis of β3 -homo-amino acids. Isomeric optically pure Fmoc and Boc β3 -homo-amino acids were prepared in two-step Arndt-Eistert homologation of N-protected amino acids. The α,β-hybrides of DT I were synthesized by manual solid-phase peptide synthesis (SPPS) using standard techniques. The α,βhybrides of tetrapeptides and biphalin were synthesized in solution. The opioid analogues containing β3 -homo-amino acids were for µ and δ-opioid receptors affinity.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.163

Twórcy

autor

Olma A.

• Institue of Organic Chemistry, Technical University of Lodz, Lodz, Poland

autor

Podwysocka D.

• Institue of Organic Chemistry, Technical University of Lodz, Lodz, Poland

autor

Lipkowski A.W.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Kosson P.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland