The DOI matches its Crossref record; 216 of the 216 references it cites were found in a registry or an index.
Factors affecting the physical stability (aggregation) of peptide therapeutics
Open accessAbstract
The number of biological therapeutic agents in the clinic and development pipeline has increased dramatically over the last decade and the number will undoubtedly continue to increase in the coming years. Despite this fact, there are considerable challenges in the development, production and formulation of such biologics particularly with respect to their physical stabilities. There are many cases where self-association to form either amorphous aggregates or highly structured fibrillar species limits their use. Here, we review the numerous factors that influence the physical stability of peptides including both intrinsic and external factors, wherever possible illustrating these with examples that are of therapeutic interest. The effects of sequence, concentration, pH, net charge, excipients, chemical degradation and modification, surfaces and interfaces, and impurities are all discussed. In addition, the effects of physical parameters such as pressure, temperature, agitation and lyophilization are described. We provide an overview of the structures of aggregates formed, as well as our current knowledge of the mechanisms for their formation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The amyloid state and its association with protein misfolding diseases.
Knowles, T. P. J., Vendruscolo, M., & Dobson, C. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3810 · Cited by 2,382
The Amyloid State of Proteins in Human Diseases
Eisenberg, D., & Jucker, M. (2012) · Cell · doi:10.1016/j.cell.2012.02.022 · Cited by 1,744
Understanding protein adsorption phenomena at solid surfaces
Rabe, M., Verdes, D., & Seeger, S. (2011) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2010.12.007 · Cited by 1,664
Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins
Fernandez-Escamilla, A.-M., Rousseau, F., Schymkowitz, J., & Serrano, L. (2004) · Nature Biotechnology · doi:10.1038/nbt1012 · Cited by 1,658
Stability of Protein Pharmaceuticals: An Update
Manning, M. C., Chou, D. K., Murphy, B. M., Payne, R. W., & Katayama, D. S. (2010) · Pharmaceutical Research · doi:10.1007/s11095-009-0045-6 · Cited by 1,098
Protein drug stability: a formulation challenge
Frokjaer, S., & Otzen, D. E. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1695 · Cited by 1,096
Stability of Protein Pharmaceuticals
Manning, M. C., Patel, K., & Borchardt, R. T. (1989) · Pharmaceutical Research · doi:10.1023/a:1015929109894 · Cited by 1,078
Rationalization of the effects of mutations on peptide andprotein aggregation rates
Chiti, F., Stefani, M., Taddei, N., Ramponi, G., & Dobson, C. M. (2003) · Nature · doi:10.1038/nature01891 · Cited by 1,072
AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides
Conchillo-Solé, O., de Groot, N. S., Avilés, F. X., Vendrell, J., Daura, X., & Ventura, S. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-65 · Cited by 1,068
Instability, stabilization, and formulation of liquid protein pharmaceuticals
Wang, W. (1999) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(99)00152-0 · Cited by 1,064
Cited by
Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines
Xiao, W., Jiang, W., Chen, Z., Huang, Y., Mao, J., Zheng, W., Hu, Y., & Shi, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02107-5 · Cited by 449
Prebiotic Peptides: Molecular Hubs in the Origin of Life
Frenkel-Pinter, M., Samanta, M., Ashkenasy, G., & Leman, L. J. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00664 · Cited by 354
Aggregation of Protein Therapeutics Enhances Their Immunogenicity: Causes and Mitigation Strategies
Lundahl, M. L. E., Fogli, S., Colavita, P. E., & Scanlan, E. M. (2021) · RSC Chemical Biology · doi:10.1039/d1cb00067e · Cited by 212
Metadata
- Authors
- Zapadka, K. L., Becher, F. J., Gomes dos Santos, A. L., & Jackson, S. E.
- Venue
- Interface Focus
- Publisher
- The Royal Society
- Published
- 2017-10-20
- Volume
- 7
- Issue
- 6
- Pages
- 20170030
- ISSN
- 2042-8898 (ISSN-L)
- 2042-8901
- OpenAlex
- W2765546463
- Cited by
- 401
- References
- 216
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Factors affecting the physical stability (aggregation) of peptide therapeutics. https://app.cochat.ai/papers/10.1098/rsfs.2017.0030
- The paper
- Zapadka, K. L., Becher, F. J., Gomes dos Santos, A. L., & Jackson, S. E. (2017). Factors affecting the physical stability (aggregation) of peptide therapeutics. Interface Focus. https://doi.org/10.1098/rsfs.2017.0030
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
