Mechanism for long-acting chimeras based on fusion with the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin beta-subunit 3

TL;DR

This paper presents a semi-quantitative thermodynamic scaling theory explaining how fusion with the CTP of human chorionic gonadotropin beta-subunit extends the lifetime and enhances functionality of human growth proteins in vivo.

Contribution

It introduces a no-parameter model that explains the increased stability and activity of CTP-fused proteins through hydrophilic terminal spheres affecting membrane interactions.

Findings

CTP fusion extends protein lifetime in vivo.

Hydrophilic terminal spheres influence membrane orientation.

The theory is semi-quantitative with no adjustable parameters.

Abstract

Thermodynamic scaling explains the dramatic successes of CTP fused human growth proteins as regards lifetime in vivo and enhanced functionality compared to their wild-type analogues, like Biogen. The theory is semi-quantitative and contains no adjustable parameters. It shows how hydrophilic terminal spheres orient fused proteins in the neighborhood of a membrane surface, extending lifetimes and improving functionality.