Deamidation of model β-turn cyclic peptides in the solid state

Krogmeier, Stephanie L.; Reddy, D. Srinivasa; Velde, David Vander; Lushington, Gerald H.; Siahaan, Teruna J.; Middaugh, C. Russell; Borchardt, Ronald T.; Topp, Elizabeth M.

doi:10.1002/jps.20468

Cited by 10 publications

(6 citation statements)

References 25 publications

(32 reference statements)

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“…In addition, a number of studies have shown that placement of the reactive Asn residue within an ordered secondary structure slows the reaction rate. This has been found for α-helices (33,34), β-sheets (35), and β-turns (36,37).…”

Section: Effect Of Higher Order Structure On Asn Deamidationmentioning

confidence: 89%

“…Briefly, many of the reactions described here, including deamidation, have been observed for polypeptides in the solid state as well. For example, the deamidation rates of both cyclic and linear peptides were investigated in the solid state (37). A comparison of deamidation rates between solution and in the solid state can be found as well (96).…”

Section: Deamidation In the Solid Statementioning

confidence: 99%

See 1 more Smart Citation

Stability of Protein Pharmaceuticals: An Update

Manning¹,

Chou²,

Murphy³

et al. 2010

Pharm Res

1,001

782

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In 1989, Manning, Patel, and Borchardt wrote a review of protein stability (Manning et al., Pharm. Res. 6:903-918, 1989), which has been widely referenced ever since. At the time, recombinant protein therapy was still in its infancy. This review summarizes the advances that have been made since then regarding protein stabilization and formulation. In addition to a discussion of the current understanding of chemical and physical instability, sections are included on stabilization in aqueous solution and the dried state, the use of chemical modification and mutagenesis to improve stability, and the interrelationship between chemical and physical instability.

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Section: Effect Of Higher Order Structure On Asn Deamidationmentioning

confidence: 89%

Section: Deamidation In the Solid Statementioning

confidence: 99%

Stability of Protein Pharmaceuticals: An Update

Manning¹,

Chou²,

Murphy³

et al. 2010

Pharm Res

1,001

782

View full text Add to dashboard Cite

show abstract

“…Many studies have looked at the effect of conformation and structure on the chemical degradation rates of model peptides, and this has strongly shaped our current understanding of these processes. [158][159][160][161][162][163][164][165][166][167][168][169][170][171][172] It is necessary, however, to further probe the finer details of the relationships between chemical degradation and protein dynamics using varying timescales and the idea that proteins are statistical distributions of conformational microstates with varying degrees of flexibility.…”

Section: Protein Flexibility and Chemical Stabilitymentioning

confidence: 99%

The Complex Inter-Relationships Between Protein Flexibility and Stability

Kamerzell¹,

Middaugh²

2008

Journal of Pharmaceutical Sciences

108

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“…Additionally, substitution of these amino acids with unnatural analogs such as nitro or fluorinated side groups could also result in similar, if not better, performing properties. We are currently looking towards the use of cyclic peptides to provide even greater stability, since the rate of such intramolecular reactions is greatly reduced, and the cyclic peptides tend to yield higher affinities and selectivities from even fewer screening steps …”

Section: Discussionmentioning

confidence: 99%

Protein catalyzed capture agents with tailored performance for in vitro and in vivo applications

et al. 2017

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We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T 1/2 ) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 1008C, and > 81% binding activity for PA after heating at 908C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives.

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Deamidation of model β-turn cyclic peptides in the solid state

Cited by 10 publications

References 25 publications

Stability of Protein Pharmaceuticals: An Update

Stability of Protein Pharmaceuticals: An Update

The Complex Inter-Relationships Between Protein Flexibility and Stability

Protein catalyzed capture agents with tailored performance for in vitro and in vivo applications

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