Progress toward a peptidomimetic of laminin-derived pentapeptide YIGSR: synthesis of the unique tricyclic core structure.
The peptide sequence YIGSR, a segment of the basement membrane matrix glycoprotein laminin, has been identified as a key component in tumor cell invasion. Guided by extensive NMR work and de novo design algorithms, a nonpeptide mimetic of this pentapeptide was identified as a lead candidate for synthesis. The target displays the key amino acid side chains from a novel tricyclic scaffold. The first synthesis of this unique scaffold is completed in 11 steps and 7% overall yield.
Busqué
Félix
F
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Hopkins
Stephanie A
SA
Konopelski
Joseph P
JP
D000465:Algorithms; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002625:Chemistry, Organic / Q000379:methods; D007797:Laminin / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*
C470965:CDPGYIGSR; D007797:Laminin; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine