Polypeptide Conjugate Binders for Protein Recognition

  • Lars Baltzer
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 277)


A new class of hybrid molecules for protein recognition is presented, where polypeptides are covalently linked to small organic molecules to form polypeptide conjugates that bind proteins with high affinity and selectivity. To illustrate the concept, a binder for human carbonic anhydrase II with a dissociation constant of 4 nM is described. The affinity of the polypeptide conjugate arises from cooperativity in binding between a benzenesulfonamide residue, with a dissociation constant of 1.5 μM, and the polypeptide scaffold with a dissociation constant of <1  mM. The combination of a ligand with moderate affinity for a target protein with a polypeptide relaxes considerably the need for high affinity on the part of the polypeptide, and thus the need for structural complexity and preorganization. At the same time, the requirement for high affinity on the part of ligand is relaxed. As a consequence, the time for development of robust, high affinity, selective binder is shortened. The chemical approach to protein recognition provides well-defined molecular entities that are conveniently handled, stored and site-specifically functionalized.

Affinity Conjugate Molecular recognition Polypeptide Protein 


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© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  1. 1.Department of Biochemistry and Organic ChemistryUppsala University, BMCUppsalaSweden

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