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Incorporation of thioether building blocks into an α v β 3 ‐specific RGD peptide: Synthesis and biological activity
Author(s) -
Kelleman Audrey,
Mattern RalphHeiko,
Pierschbacher Michael D.,
Goodman Murray
Publication year - 2003
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10586
Subject(s) - thioether , chemistry , peptide , stereochemistry , receptor , affinities , combinatorial chemistry , beta (programming language) , binding affinities , disulfide bond , chemical synthesis , alpha (finance) , biochemistry , in vitro , medicine , construct validity , nursing , computer science , patient satisfaction , programming language
We report the design, synthesis, and binding affinities of a family of thioether analogues of the α v β 3 ‐specific compound c[(Mpa)RGDD( t BuG)C]‐NH 2 . The synthesis of the thioether building blocks is scalable and produced the desired products in good yields. The linear peptides were synthesized on solid supports, followed by cyclization in solution. Our analogues demonstrate interesting binding data to the isolated receptors. In particular, the peptide c[NH‐Arg‐Gly‐Asp‐Asp‐( t BuG)‐Cys(S‐CH 2 ‐CO)]NH 2 ( 1 ) exhibits differences in binding when compared to the parent compound and demonstrates potent affinity to the α v β 3 and α 5 β 1 receptors while having reduced binding to the α IIb β 3 receptor. This result combined with the replacement of the disulfide with a thioether makes this compound interesting for further development. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003