Albumin affinity tags increase peptide half-life in vivo

Koehler, Michael F. T.; Zobel, Kerry; Beresini, Maureen H.; Caris, Lisa D.; Combs, Daniel L.; Paasch, Brian D.; Lazarus, Robert A.

doi:10.1016/s0960-894x(02)00610-8

Cited by 61 publications

(55 citation statements)

References 14 publications

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“…Albumin is known to exhibit a longer t 1/2 in vivo, ϳ19 days in humans (40), which is much greater than the t 1/2 of short-lived regulatory peptides such as GLP-1. Accordingly, peptide binding to albumin has been used to improve the pharmacokinetic properties of several smaller proteins, including Fab antibody fragments (33), coagulation factor VIIa inhibitor 1a (41), and insulin (42). Several experimental results provide indirect evidence for a sustained duration of CJC-1131 action on glucose lowering in vivo.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Glucagon-Like Peptide 1-Albumin Conjugate

Kim

Baggio²,

Bridon³

et al. 2003

Diabetes

204

115

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Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Glucagon-Like Peptide 1-Albumin Conjugate

Kim

Baggio²,

Bridon³

et al. 2003

Diabetes

204

115

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“…Similarly, fusion of the amino acid sequence of human growth hormone to albumin prolonged the circulating t 1/2 of Albutropin relative to the native growth hormone, yet Albutropin retained the ability to stimulate IGF-I and body weight gain in vivo (28). Moreover, peptide binding to albumin extended the pharmacokinetic properties of several smaller proteins including insulin (29), Fab antibody fragments (26), and coagulation factor VIIa inhibitor 1a (30). In contrast to Albugon, however, these albumin-peptide derivatives exert their predominant actions outside the CNS, and activation of the CNS is not critical for their therapeutic actions.…”

Section: Diabetes Vol 53 September 2004mentioning

confidence: 99%

A Recombinant Human Glucagon-Like Peptide (GLP)-1–Albumin Protein (Albugon) Mimics Peptidergic Activation of GLP-1 Receptor–Dependent Pathways Coupled With Satiety, Gastrointestinal Motility, and Glucose Homeostasis

et al. 2004

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Peptide hormones exert unique actions via specific G protein-coupled receptors; however, the therapeutic potential of regulatory peptides is frequently compromised by rapid enzymatic inactivation and clearance from the circulation. In contrast, recombinant or covalent coupling of smaller peptides to serum albumin represents an emerging strategy for extending the circulating t 1/2 of the target peptide. However, whether larger peptide-albumin derivatives will exhibit the full spectrum of biological activities encompassed by the native peptide remains to be demonstrated. We report that Albugon, a human glucagon-like peptide (

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“…In contrast, RITA did not associate with human fibrinogen (Figure 1C), suggesting a selective interaction with p53. Human serum albumin (HSA), known blood carrier of various drugs (Koehler et al 2002), served as binding control ( Figure 1C). Under denaturating conditions [ …”

Section: Interaction Of Rita With the N-terminus Of P53mentioning

confidence: 99%

Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy

Zawacka-Pankau

Burmakin

et al. 2018

Preprint

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Given the immense significance of p53 restoration for anti-cancer therapy, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in p53 regulation, whose targeting by RITA, PpIX and licofelone block the binding of p53 inhibitors, MDM2 and MDMX. Deletion and mutation analysis followed by molecular modeling, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators. Our study provides the basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacological potential.

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Albumin affinity tags increase peptide half-life in vivo

Cited by 61 publications

References 14 publications

Development and Characterization of a Glucagon-Like Peptide 1-Albumin Conjugate

Development and Characterization of a Glucagon-Like Peptide 1-Albumin Conjugate

A Recombinant Human Glucagon-Like Peptide (GLP)-1–Albumin Protein (Albugon) Mimics Peptidergic Activation of GLP-1 Receptor–Dependent Pathways Coupled With Satiety, Gastrointestinal Motility, and Glucose Homeostasis

Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy

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