title: Conjugation of a Dipicolyl Chelate to Polypeptide Conjugates Increases Binding Affinities for Human Serum Albumin and Survival Times in Human Serum.
abstract: The affinity for human serum albumin (HSA) of a series of 2-5 kDa peptides covalently linked to 3,5-bis[[bis(2-pyridylmethyl)amino]methyl]benzoic acid, a dipicolyl chelator with micromolar affinity for Zn2+, was found by surface plasmon resonance to increase in the presence of 1 μm ZnCl2at physiological pH. The dependence on polypeptide hydrophobicity was found to be minor, thus suggesting that the conjugates bound to the metal-binding site and not to the fatty-acid-binding site. The affinity of the conjugates increased strongly with the positive charge of the polypeptides, thus implicating the negatively charged protein surface surrounding the metal-binding site. The survival times of the peptides in human serum were extended as a consequence of stronger binding to HSA, thus suggesting that Zn2+-chelating agents might provide a general route to increased survival time of peptides in serum in therapeutic and diagnostic applications without significantly increasing their molecular weights.
authors.affiliation: Department of Chemistry-BMC, Uppsala University, PO. Box 576, 751 23, Uppsala, Sweden.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Balliu
authors.affiliation: Department of Chemistry-BMC, Uppsala University, PO. Box 576, 751 23, Uppsala, Sweden.
authors.forename: Lars
authors.identifier: 0000-0001-5807-2726
authors.initials: L
authors.lastname: Baltzer
mesh_terms: D001565:Benzoates / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D013997:Time Factors; D015032:Zinc / Q000737:chemistry*
chemical_list: C000623200:3,5-bis((bis(2-pyridylmethyl)amino)methyl)benzoic acid; D001565:Benzoates; D002614:Chelating Agents; D010455:Peptides; D011725:Pyridines; D012709:Serum Albumin; D015032:Zinc
keywords: affinity; biosensor; human serum albumin; peptides; zinc-binding site