Conformational Dynamics in Extended RGD-Containing Peptides.

Autor:	Lindemann WR; Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States., Mijalis AJ; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States., Alonso JL; Leukocyte Biology and Inflammation Program, Division of Nephrology and Department of Medicine, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, United States.; Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, United States., Borbat PP; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States., Freed JH; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States., Arnaout MA; Leukocyte Biology and Inflammation Program, Division of Nephrology and Department of Medicine, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, United States.; Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, United States., Pentelute BL; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States., Ortony JH; Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Jazyk:	angličtina
Zdroj:	Biomacromolecules [Biomacromolecules] 2020 Jul 13; Vol. 21 (7), pp. 2786-2794. Date of Electronic Publication: 2020 Jun 16.
DOI:	10.1021/acs.biomac.0c00506
Abstrakt:	RGD is a prolific example of a tripeptide used in biomaterials for cell adhesion, but the potency of free or surface-bound RGD tripeptide is orders-of-magnitude less than the RGD domain within natural proteins. We designed a set of peptides with varying lengths, composed of fragments of fibronectin protein whose central three residues are RGD, in order to vary their conformational behavior without changing the binding site's chemical environment. With these peptides, we measure the conformational dynamics and transient structure of the active site. Our studies reveal how flanking residues affect conformational behavior and integrin binding. We find that disorder of the binding site is important to the potency of RGD peptides and that transient hydrogen bonding near the RGD site affects both the energy landscape roughness of the peptides and peptide binding. This phenomenon is independent of longer-range folding interactions and helps explain why short binding sequences, including RGD itself, do not fully replicate the integrin-targeting properties of extracellular matrix proteins. Our studies reinforce that peptide binding is a holistic event and fragments larger than those directly involved in binding should be considered in the design of peptide epitopes for functional biomaterials.
Databáze:	MEDLINE
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