Neoglycolipids for Prolonging the Effects of Peptides: Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Neoglycolipids for Prolonging the Effects of Peptides : Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy. / van Witteloostuijn, Søren Blok; Mannerstedt, Karin Margareta Sophia; Wismann, Pernille; Bech, Esben Matzen; Thygesen, Mikkel Boas; Vrang, Niels; Jelsing, Jacob; Jensen, Knud Jørgen; Pedersen, Søren Ljungberg.

In: Molecular Pharmaceutics, Vol. 14, No. 1, 2017, p. 193-205.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

van Witteloostuijn, SB, Mannerstedt, KMS, Wismann, P, Bech, EM, Thygesen, MB, Vrang, N, Jelsing, J, Jensen, KJ & Pedersen, SL 2017, 'Neoglycolipids for Prolonging the Effects of Peptides: Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy', Molecular Pharmaceutics, vol. 14, no. 1, pp. 193-205. https://doi.org/10.1021/acs.molpharmaceut.6b00787

APA

van Witteloostuijn, S. B., Mannerstedt, K. M. S., Wismann, P., Bech, E. M., Thygesen, M. B., Vrang, N., Jelsing, J., Jensen, K. J., & Pedersen, S. L. (2017). Neoglycolipids for Prolonging the Effects of Peptides: Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy. Molecular Pharmaceutics, 14(1), 193-205. https://doi.org/10.1021/acs.molpharmaceut.6b00787

Vancouver

van Witteloostuijn SB, Mannerstedt KMS, Wismann P, Bech EM, Thygesen MB, Vrang N et al. Neoglycolipids for Prolonging the Effects of Peptides: Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy. Molecular Pharmaceutics. 2017;14(1):193-205. https://doi.org/10.1021/acs.molpharmaceut.6b00787

Author

van Witteloostuijn, Søren Blok ; Mannerstedt, Karin Margareta Sophia ; Wismann, Pernille ; Bech, Esben Matzen ; Thygesen, Mikkel Boas ; Vrang, Niels ; Jelsing, Jacob ; Jensen, Knud Jørgen ; Pedersen, Søren Ljungberg. / Neoglycolipids for Prolonging the Effects of Peptides : Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy. In: Molecular Pharmaceutics. 2017 ; Vol. 14, No. 1. pp. 193-205.

Bibtex

@article{affda309455c462cae633765ab94e896,
title = "Neoglycolipids for Prolonging the Effects of Peptides: Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy",
abstract = "Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug candidates for treatment of type 2 diabetes and obesity. Neoglycolipidation of GLP-1 balanced the lipophilicity, directed formation of soluble oligomers, and mediated albumin binding. Moreover, neoglycolipidation did not compromise bioactivity, as in vitro potency of neoglycolipidated GLP-1 analogues was maintained or even improved compared to native GLP-1. This translated into pronounced in vivo efficacy in terms of both decreased acute food intake and improved glucose homeostasis in mice. Thus, we propose neoglycolipidation as a novel, general method for modulating the properties of therapeutic peptides",
keywords = "neoglycolipid, lipidation, glucagon-like peptide 1, glycolipid, half-life extension, biopharmaceutical, peptide",
author = "{van Witteloostuijn}, {S{\o}ren Blok} and Mannerstedt, {Karin Margareta Sophia} and Pernille Wismann and Bech, {Esben Matzen} and Thygesen, {Mikkel Boas} and Niels Vrang and Jacob Jelsing and Jensen, {Knud J{\o}rgen} and Pedersen, {S{\o}ren Ljungberg}",
year = "2017",
doi = "10.1021/acs.molpharmaceut.6b00787",
language = "English",
volume = "14",
pages = "193--205",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "1",

}

RIS

TY - JOUR

T1 - Neoglycolipids for Prolonging the Effects of Peptides

T2 - Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy

AU - van Witteloostuijn, Søren Blok

AU - Mannerstedt, Karin Margareta Sophia

AU - Wismann, Pernille

AU - Bech, Esben Matzen

AU - Thygesen, Mikkel Boas

AU - Vrang, Niels

AU - Jelsing, Jacob

AU - Jensen, Knud Jørgen

AU - Pedersen, Søren Ljungberg

PY - 2017

Y1 - 2017

N2 - Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug candidates for treatment of type 2 diabetes and obesity. Neoglycolipidation of GLP-1 balanced the lipophilicity, directed formation of soluble oligomers, and mediated albumin binding. Moreover, neoglycolipidation did not compromise bioactivity, as in vitro potency of neoglycolipidated GLP-1 analogues was maintained or even improved compared to native GLP-1. This translated into pronounced in vivo efficacy in terms of both decreased acute food intake and improved glucose homeostasis in mice. Thus, we propose neoglycolipidation as a novel, general method for modulating the properties of therapeutic peptides

AB - Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug candidates for treatment of type 2 diabetes and obesity. Neoglycolipidation of GLP-1 balanced the lipophilicity, directed formation of soluble oligomers, and mediated albumin binding. Moreover, neoglycolipidation did not compromise bioactivity, as in vitro potency of neoglycolipidated GLP-1 analogues was maintained or even improved compared to native GLP-1. This translated into pronounced in vivo efficacy in terms of both decreased acute food intake and improved glucose homeostasis in mice. Thus, we propose neoglycolipidation as a novel, general method for modulating the properties of therapeutic peptides

KW - neoglycolipid

KW - lipidation

KW - glucagon-like peptide 1

KW - glycolipid

KW - half-life extension

KW - biopharmaceutical

KW - peptide

U2 - 10.1021/acs.molpharmaceut.6b00787

DO - 10.1021/acs.molpharmaceut.6b00787

M3 - Journal article

C2 - 28005376

VL - 14

SP - 193

EP - 205

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 1

ER -

ID: 176369858