High-affinity recognition of the human C-reactive protein independent of phosphocholine

Organic & Biomolecular Chemistry
Jie YangLars Baltzer

Abstract

A high-affinity polypeptide conjugate 4-C25L22-DQ, has been developed for the molecular recognition of the human C-reactive protein, CRP, a well-known inflammation biomarker. CRP is one of the most frequently quantified targets in diagnostic applications and a target in drug development. With the exception of antibodies, most molecular constructs take advantage of the known affinity for CRP of phosphocholine that depends on Ca2+ for its ability to bind. 4-C25L22-DQ which is unrelated to phosphocholine binds in the absence of Ca2+ with a dissociation constant of 760 nM, an order of magnitude lower than that of phosphocholine, the KD of which is 5 μM. The small organic molecule 2-oxo-1,2-dihydroquinoline-8-carboxylic acid (DQ) was designed based on the structural similarities between three hits from a set of compounds selected from a building block collection and evaluated with regards to affinity for CRP by NMR spectroscopy. 4-C25L22-DQ was shown in a competition experiment to bind CRP three orders of magnitude more strongly than DQ itself, and in a pull-down experiment 4-C25L22-DQ was shown to extract CRP from human serum. The development of a robust and phosphocholine-independent recognition element provides unprecedented oppo...Continue Reading

References

Jun 14, 2000·Annals of Medicine·T W Du Clos
Sep 5, 2001·Molecular Immunology·J E Volanakis
Aug 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·K Peter R NilssonOlle Inganäs
Nov 22, 2005·Chemistry & Biology·Theresa AnderssonLars Baltzer

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Citations

Feb 12, 2020·Quarterly Reviews of Biophysics·Ivan V Korendovych, William F DeGrado

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