Selectively N-Methylated Soluble IAPP Mimics as Potent IAPP Receptor Agonists and Nanomolar Inhibitors of Cytotoxic Self-Assembly of Both IAPP and Aβ40

被引：42

作者：

Yan, Li-Mei ^{[1
]}

Velkova, Aleksandra ^{[1
]}

Tatarek-Nossol, Marianna ^{[2
]}

Rammes, Gerhard ^{[3
]}

Sibaev, Andrei ^{[4
]}

Andreetto, Erika ^{[1
]}

Kracklauer, Michael ^{[1
]}

Bakou, Maria ^{[1
,2
]}

Malideli, Eleni ^{[1
]}

Goeke, Burkhard ^{[4
]}

Schirra, Joerg ^{[4
]}

Storr, Martin ^{[4
]}

Kapurniotu, Aphrodite ^{[1
]}

机构：

[1] Tech Univ Munich, Div Peptide Biochem, D-85354 Freising Weihenstephan, Germany

[2] Rhein Westfal TH Aachen, Inst Biochem & Mol Cell Biol, Aachen, Germany

[3] Tech Univ Munich, Klinikum Rechts Isar, Dept Anesthesiol, D-81675 Munich, Germany

[4] Klinikum Univ Munchen Grosshadern, Med Klin & Poliklin 2, D-81377 Munich, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2013年 / 52卷 / 39期

关键词：

IAPP receptor agonist; islet amyloid polypeptide; protein interactions; self-assembly; -amyloid peptide; ISLET AMYLOID POLYPEPTIDE; A-BETA; ALZHEIMERS-DISEASE; BINDING-SITES; AMYLIN; IDENTIFICATION; FIBRILLOGENESIS; MECHANISM; TOXICITY; FIBRILS;

D O I：

10.1002/anie.201302840

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The selective incorporation of N-methyl groups in the highly amyloidogenic and cytotoxic sequence of the type 2 diabetes islet amyloid polypeptide (IAPP) generates a unique class of soluble and nontoxic IAPP mimics. These polypeptides combine potent IAPP receptor agonism with nanomolar-affinity inhibitory potential on the amyloid formation and cell-damaging effects of both IAPP and the Alzheimer's β-amyloid peptide (Aβ40). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：10378 / 10383

页数：6

共 38 条

[1] A single-point mutation converts the highly amyloidogenic human islet amyloid polypeptide into a potent fibrillization inhibitor [J].

Abedini, Andisheh ;

Meng, Fanling ;

Raleigh, Daniel P. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (37) :11300-+

[2] Diabetes mellitus and Alzheimer's disease: shared pathology and treatment? [J].

Akter, Kawser ;

Lanza, Emily A. ;

Martin, Stephen A. ;

Myronyuk, Natalie ;

Rua, Melanie ;

Raffa, Robert B. .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 71 (03) :365-376

[3] Dissecting the Role of Single Regions of an IAPP Mimic and IAPP in Inhibition of Aβ40 Amyloid Formation and Cytotoxicity [J].

Andreetto, Erika ;

Yan, Li-Mei ;

Caporale, Andrea ;

Kapurniotu, Aphrodite .

CHEMBIOCHEM, 2011, 12 (09) :1313-1322

[4] Identification of Hot Regions of the Aβ-IAPP Interaction Interface as High-Affinity Binding Sites in both Cross- and Self-Association [J].

Andreetto, Erika ;

Yan, Li-Mei ;

Tatarek-Nossol, Marianna ;

Velkova, Aleksandra ;

Frank, Ronald ;

Kapurniotu, Aphrodite .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2010, 49 (17) :3081-3085

[5]

[Anonymous], 2010, ANGEW CHEM

[6] Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes [J].

Bailey, R. J. ;

Walker, C. S. ;

Ferner, A. H. ;

Loomes, K. M. ;

Prijic, G. ;

Halim, A. ;

Whiting, L. ;

Phillips, A. R. J. ;

Hay, D. L. .

BRITISH JOURNAL OF PHARMACOLOGY, 2012, 166 (01) :151-167

[7] N-Methylation of Peptides: A New Perspective in Medicinal Chemistry [J].

Chatterjee, Jayanta ;

Gilon, Chaim ;

Hoffman, Amnon ;

Kessler, Horst .

ACCOUNTS OF CHEMICAL RESEARCH, 2008, 41 (10) :1331-1342

[8] The Amyloid Formation Mechanism in Human IAPP: Dimers Have β-Strand Monomer-Monomer Interfaces [J].

Dupuis, Nicholas F. ;

Wu, Chun ;

Shea, Joan-Emma ;

Bowers, Michael T. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (19) :7240-7243

[9] Inhibition of β-amyloid(40) fibrillogenesis and disassembly of β-amyloid(40) fibrils by short β-amyloid congeners containing N-methyl amino acids at alternate residues [J].

Gordon, DJ ;

Sciarretta, KL ;

Meredith, SC .

BIOCHEMISTRY, 2001, 40 (28) :8237-8245

[10] Gastric emptying in diabetes: clinical significance and treatment [J].

Horowitz, M ;

O'Donovan, D ;

Jones, KL ;

Feinle, C ;

Rayner, CK ;

Samsom, M .

DIABETIC MEDICINE, 2002, 19 (03) :177-194

← 1 2 3 4 →