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SUMMARY:Conformational Analysis of Kyotorphin Analogues Containing Unnatur
 al Amino Acids
DTSTART;VALUE=DATE-TIME:20121018T134500Z
DTEND;VALUE=DATE-TIME:20121018T150000Z
DTSTAMP;VALUE=DATE-TIME:20261011T042449Z
UID:indico-contribution-158@indico.ipb.ac.rs
DESCRIPTION:Speakers: Nicolay Dodoff (Roumen Tsanev Institute of Molecular
  Biology\, Bulgarian Academy of Sciences\, 1113 Sofia\, Bulgaria)\nThe dip
 eptide kyotorphin (Tyr-Arg\, Kyo) plays a role in pain modulation in the m
 ammalian central nervous system (CNS)\, and is one of the most investigate
 d neuropeptides. The Tyr-Arg motif exists widely throughout the brain not 
 only as kyotorphin\, but also as the N-terminal part of several endogenous
  analgesic peptides1\,2. Also\, this peptide is very rapidly degraded by a
 minopeptidases3. One of the successful strategies in the design of neurope
 ptides with enhanced stability and improved delivery to the CNS is that wi
 th the use of non-protein amino acids\, like canavanive (Cav)\, a structur
 al analogue and antimetabolite of arginine (Arg). In our previous in vivo 
 experiments we demonstrated that Tyr-Cav exerted a strong-reversible analg
 esic effect\, more pronounced than that of Kyo. Bearing in mind these and 
 the fact that norsulfoarginine (NsArg)4 is a structural analogue of argini
 ne and canavanine\, we synthesized a series of new peptides with expected 
 analgesic activity\, containing NsArg residues in their molecules: NsArg-T
 yr\, Tyr-NsArg\, Tyr-NsArg-NH2 and Tyr-NsArg-OBzl5\,6. \nThe conformationa
 l features of these dipeptides are of particular interest\, both from theo
 retical and pharmacological point of view. Since no single-crystal X-ray d
 iffraction data for the compounds are available until now\, we undertook a
  quantum-chemical modelling of their structure. \nWe have undertaken a pro
 found conformational study of kyotorphin and its synthetic analogues\, con
 taining unnatural amino acid nor-sulfoarginine (NsArg). \nHere we present 
 our preliminary computational results for Kyo\, NsArg-Tyr аnd Tyr-NsArg. 
 Molecular mechanics (MM+ force field) conformational search for the two sp
 ecies was performed\, and the global minimum-energy conformations thus obt
 ained\, were further optimized at HF ab initio (3-21G** basis set) level o
 f theory. In the three cases (Kyo\, NsArg-Tyr\, and Tyr-NsArg) specific\, 
 scorpion-like conformations are realized\, with hydrogen bonds involving t
 he guanidino-group and the phenolic hydroxyl. Numerical results are obtain
 ed using HPC cluster deployed at the Institute of Information and Communic
 ation Technologies. This cluster is part of High-Performance Computing Inf
 rastructure for South East Europe’s Research Communities.\n\nhttps://eve
 nts.saifa.rs/event/291/contributions/158/
LOCATION:National Library of Serbia
URL:https://events.saifa.rs/event/291/contributions/158/
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