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"Human and Mouse Cross-Reactive" Albumin-Binding Helix-Loop-Helix Peptide Tag for Prolonged Bioactivity of Therapeutic Proteins.

ABSTRACT: The effectiveness of protein and peptide pharmaceuticals depends essentially on their intrinsic pharmacokinetics. Small-sized pharmaceuticals in particular often suffer from short serum half-lives due to rapid renal clearance. To improve the pharmacokinetics by association with serum albumin (SA) in vivo, we generated an SA-binding tag of a helix-loop-helix (HLH) peptide to be linked with protein pharmaceuticals. For use in future preclinical studies, screening of yeast-displayed HLH peptide libraries against human SA (HSA) and mouse SA (MSA) was alternately repeated to give the SA-binding peptide AY-VE, which exhibited cross-binding activities to HSA and MSA with K_D of 65 and 20 nM, respectively. As a proof of concept, we site-specifically conjugated peptide AY-VE with insulin to examine its bioactivity in vivo. In mouse bioassay monitoring the blood glucose level, the AY-VE conjugate was found to have a prolonged hypoglycemic effect for 12 h. The HLH peptide tag is a general platform for extending the bioactivity of therapeutic peptides or proteins.

SUBMITTER: Nakatani Y

PROVIDER: S-EPMC9257745 | biostudies-literature |

REPOSITORIES: biostudies-literature

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An overview of the basic helix-loop-helix proteins.

Project description:The basic helix-loop-helix proteins are dimeric transcription factors that are found in almost all eukaryotes. In animals, they are important regulators of embryonic development, particularly in neurogenesis, myogenesis, heart development and hematopoiesis.

| S-EPMC463060 | biostudies-literature

Phylogenetic analysis of the human basic helix-loop-helix proteins.

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| S-EPMC116727 | biostudies-literature

E Proteins and ID Proteins: Helix-Loop-Helix Partners in Development and Disease.

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Origin and diversification of basic-helix-loop-helix proteins in plants.

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| S-EPMC84258 | biostudies-literature

Salvador-Warts-Hippo pathway in a developmental checkpoint monitoring helix-loop-helix proteins.

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| S-EPMC4308471 | biostudies-literature

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| S-EPMC307222 | biostudies-other

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Project description:A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.

| S-EPMC360994 | biostudies-other

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