Incorporation of thioether building blocks into an αvβ3-specific RGD peptide: Synthesis and biological activity

We report the design, synthesis, and binding affinities of a family of thioether analogues of the αvβ3‐specific compound c[(Mpa)RGDD(tBuG)C]‐NH2. The synthesis of the thioether building blocks is scalable and produced the desired products in good yields. The linear peptides were synthesized on solid...

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Veröffentlicht in:Peptide Science 2003, Vol.71 (6), p.686-695
Hauptverfasser: Kelleman, Audrey, Mattern, Ralph-Heiko, Pierschbacher, Michael D., Goodman, Murray
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Sprache:eng
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Zusammenfassung:We report the design, synthesis, and binding affinities of a family of thioether analogues of the αvβ3‐specific compound c[(Mpa)RGDD(tBuG)C]‐NH2. 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‐(tBuG)‐Cys(S‐CH2‐CO)]NH2 (1) exhibits differences in binding when compared to the parent compound and demonstrates potent affinity to the αvβ3 and α5β1 receptors while having reduced binding to the αIIbβ3 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
ISSN:0006-3525
1097-0282
DOI:10.1002/bip.10586