Premium
A complete substitutional analysis of VIP for better tumor imaging properties
Author(s) -
Bhargava Sarah,
Licha Kai,
Knaute Tobias,
Ebert Bernd,
Becker Andreas,
Grötzinger Carsten,
Hessenius Carsten,
Wiedenmann Bertram,
SchneiderMergener Jens,
VolkmerEngert Rudolf
Publication year - 2002
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.565
Subject(s) - vasoactive intestinal peptide , in vivo , flow cytometry , chemistry , peptide , conjugate , membrane , biophysics , receptor , biochemistry , microbiology and biotechnology , biology , neuropeptide , mathematical analysis , mathematics
Since numerous tumor cells overexpress the vasoactive intestinal peptide (VIP) receptor subtype 1 (VPAC 1 ), VIP–dye conjugates would be useful as contrast agents for in vivo imaging. However, proteolytic degradation of VIP in vivo limits their diagnostic use and highlights the need for structurally optimized VIP derivatives with improved pharmacokinetics. Here, we applied parallel nano‐synthesis of cleavable peptides on cellulose membranes to perform a complete VIP substitutional analysis. The resulting 504 different VIP–dye analogs were tested for cell binding by flow cytometry. They provided a detailed analysis of amino acid positions essential for binding to VPAC 1 overexpressing cells. A generalized VIP–dye binding motif derived from the substitutional analysis results served as a reference point for further optimization. An [Arg8]‐VIP‐dye analog showed increased stability towards proteolytic degradation, good tumor‐to‐tissue contrast in mice and a longer half‐life in vivo . Copyright © 2002 John Wiley & Sons, Ltd.