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Peptides and Peptide Analogs to Inhibit Protein-Protein Interactions

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Protein Targeting Compounds

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 917))

Abstract

Protein-protein interactions are governed by relatively few amino acid residues at the binding interface. Peptides derived from these protein regions may serve as mimics of one of the interaction partners in structural studies or as inhibitors to disrupt the respective interaction and investigate its biological consequences. Inhibitory peptides may also be lead structures for drug development if the respective protein-protein interaction is essential for a pathogen or disease mechanism. Binding peptides may be systematically derived from one of the binding partners or found in the screen of combinatorial peptide libraries. Molecular modelling based on structural data helps to refine existing peptides or even design novel binding peptides. This chapter gives an outline of the binding peptide discovery process and subsequent chemical modifications to further enhance affinity and specificity and to increase stability against degradation in vivo. Examples from the past three decades illustrate the great diversity of applications for protein binding peptides and peptide analogs.

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Abbreviations

Bag-1L:

BCL2-associated athanogene

BCL2:

B-cell lymphoma 2

BIR3:

Baculovirus inhibitor of apoptosis protein 3

BLI:

Biolayer interferometry

Boc:

tert-Butoxycarbonyl-

BSA:

Bovine serum albumin

CDK:

Cyclin-dependent kinase

CXCL8:

CXC-class chemokine ligand 8, interleukin-8

CXCR1:

CXC-class chemokine receptor, IL8RA

DIABLO:

Direct IAP binding protein with low pI, Smac

DIC:

Diisopropylcarbodiimide

DMF:

N,N-Dimethylformamide

EZH2:

Enhancer of zeste homolog 2

Fmoc:

Fluorenylmethyloxycarbonyl-

GPCR:

G-protein coupled receptor

GRP78:

Glucose responsive protein 78

HBTU:

N,N,N′,N′-Tetramethyl-O-(1H-benzotriazol-1-yl)uronium

HLA:

Human leukocyte antigen

HOBt:

Hydroxybenzotriazole

ITC:

Isothermal titration calorimetry

ML:

Multi-leucine

NMR:

Nuclear magnetic resonance

OBOC:

One-bead-one-compound

ORI:

Origin of replication

PACE4:

Paired basic amino acid cleaving enzyme 4

PC:

Proprotein convertase

PCNA:

Proliferating cell nuclear antigen

PCR:

Polymerase chain reaction

PDB:

Protein Data Bank

PSSPCL:

Positional scanning-synthetic peptide combinatorial library

PTH1R:

parathyroid hormone 1 receptor

PyBOP:

Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

RCSB:

Research Collaboratory for Structural Bioinformatics

SET:

Conserved domain in Su(var)3-9, Enhancer of zeste and Drosophila Trithorax proteins

Smac:

Second mitochondria-derived activator of caspases, DIABLO

SPPS:

Solid-phase peptide synthesis

SPR:

Surface plasmon resonance

TAR:

Transactivator response element

Tat:

Transactivator of transcription

tBu:

tert-butyl-

XIAP:

X-linked inhibitor of apoptosis

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  1. Technische Universität Darmstadt, Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Alarich-Weiss-Straße 4, 64287, Darmstadt, Germany

    Dorothea Helmer & Katja Schmitz

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  1. Recombinant protein exprsn/Intrabdy unit, Helmholtz-Centre for Infection Rese, Braunschweig, Germany

    Thomas Böldicke

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Helmer, D., Schmitz, K. (2016). Peptides and Peptide Analogs to Inhibit Protein-Protein Interactions. In: Böldicke, T. (eds) Protein Targeting Compounds. Advances in Experimental Medicine and Biology, vol 917. Springer, Cham. https://doi.org/10.1007/978-3-319-32805-8_8

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