Sticky Illusions: The Case of SGVYKVAYDWQH and the Polystyrene Trap

Abstract

SGVYKVAYDWQH consistently emerges from phage-display screens not as a genuine multitarget ligand but as a target-unrelated peptide with high affinity for polystyrene. AlphaFold predicts a compact, amphipathic a-helix that is ideal for hydrophobic surfaces, while BLASTp shows only weak, short homologies, ruling out evolutionary conservation. Reported protein or cell affinities (in the low-µM range) seldom replicate, indicating nonspecific hydrophobic binding. Therefore, plastic-free assays, hydrophobic-site mutagenesis, and solution-phase kinetics are essential to confirm any real high-affinity partners and to either utilize or avoid this peptide's stickiness in therapeutic or materials applications.

The Original Article was published on 14 April 2025.

Received: 21 August 2025 | Revised: 17 October 2025 | Accepted: 28 November 2025

Conflicts of Interest

The author declares that he has no conflicts of interest to this work.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Author Contribution Statement

Ralf Weiskirchen: Conceptualization, Validation, Formal analysis, Resources, Data curation, Writing – original draft, Writing – review & editing, Visualization, Supervision, Project administration.