C-glyco"RGD" as alpha(IIb)beta(3) and alpha(v)beta integrin ligands for imaging applications: Synthesis, in vitro evaluation and molecular modeling

The design of conjugates displaying simultaneously high selectivity and high affinity for different subtypes of integrins is a current challenge. The arginine-glycine-aspartic acid amino acid sequence (RGD) is one of the most efficient short peptides targeting these receptors. We report herein the d...

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Published inBioorganic & medicinal chemistry Vol. 27; no. 18; pp. 4101 - 4109
Main Authors Vucko, Timothe, Petry, Nicolas, Dehez, Francois, Lambert, Alexandrine, Monari, Antonio, Lakomy, Cecile, Lacolley, Patrick, Regnault, Veronique, Collet, Charlotte, Karcher, Gilles, Pellegrini-Moise, Nadia, Lamande-Langle, Sandrine
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier 15.09.2019
Subjects
Biochemistry & Molecular Biology
Chemistry
Chemistry, Medicinal
Chemistry, Organic
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physical Sciences
Science & Technology
ANGIOGENESIS
RGD PEPTIDES
CLICK CHEMISTRY
GLYCOPROTEINS
CARBOHYDRATE
GLYCOSYLATION
RGD
THIOLS
Glycopeptide
ALPHA-V-BETA-3
SMOOTH-MUSCLE-CELLS
C-Glycoside
GLYCOPEPTIDES
Integrins
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Summary:The design of conjugates displaying simultaneously high selectivity and high affinity for different subtypes of integrins is a current challenge. The arginine-glycine-aspartic acid amino acid sequence (RGD) is one of the most efficient short peptides targeting these receptors. We report herein the development of linear and cyclic fluoro-C-glycoside"RGD" conjugates, taking advantage of the robustness and hydrophilicity of C-glycosides. As attested by in vitro evaluation, the design of these C-glyco"RGD" with a flexible three-carbon triazolyl linker allows distinct profiles towards alpha(IIb)beta(3) and alpha(v)beta(3) integrins. Molecular-dynamics simulations confirm the suitability of cyclic C-glyco-c(RGDfC) to target alpha(v)beta(3) integrin. These C-glyco"RGD" could become promising biological tools in particular for Positron Emission Tomography imaging.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2019.07.039