Work

Crystallization and 1.6 Å resolution crystal structure of an acylated GLP-1/GIP analogue peptide

Year: 2026

Type: article

Abstract: With the meteoric rise in interest in GLP-1 and GIP analogue peptides in recent years, there is a drive for the use of alternative purification techniques to alleviate processing bottlenecks and reduce the cost of peptide manufacturing. However, a lack of reported crystal structures for this class of peptides has hindered molecular-scale understanding of GLP-1/GIP analogue peptide crystallization, particularly related to acylated peptides. This paper therefore reports what is believed to be the first crystal structure of a GLP-1 and GIP analogue lipopeptide. Crystals obtained using a microseed matrix-screening protocol diffracted to ≤1.6 Å resolution in space group P 4 3 , with unit-cell parameters a = b = 64.66, c = 11.42 Å. Model building and the resultant structural analysis reveals that the predominantly helical peptide forms a uniquely porous spiral crystal structure composed of clockwise-ascending monomers in a square pattern, with aromatic C...H—π interactions around Phe22 forming the primary crystal contact between neighbouring square motifs.

Source: Acta Crystallographica Section F Structural Biology Communications

DOI: 10.1107/s2053230x26001937

Authors: Hamish M. Mitchell, Boguslaw Nocek, Emily J. Guinn, Jerry Y. Y. Heng

Institutions: Imperial College London, Eli Lilly (United States)

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $3,520

Funders: Eli Lilly and Company, Engineering and Physical Sciences Research Council