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Linear and Cyclic Depsipeptidomimetics with β‐Lactam Cores: A Class of New α v β 3 Integrin Receptor Inhibitors
Author(s) -
ZabalaUncilla Nerea,
Miranda José I.,
Laso Antonio,
Fernández Xavier,
Ganboa Jose I.,
Palomo Claudio
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600642
Subject(s) - lactam , dipeptide , chemistry , integrin , stereochemistry , receptor , peptide , peptidomimetic , biochemistry , angiogenesis , combinatorial chemistry , biology , cancer research
The α v β 3 integrin receptor plays an important role in tumor metastasis and tumor‐induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe‐(Me)Val dipeptide by a β‐lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond β‐lactam‐NH‐Asp linkage by a β‐lactam‐O‐Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open‐chain compounds of the form Asp‐β‐lactam‐Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.