NDLI: Tunable helicity, stability and DNA-binding properties of short peptides with hybrid metal coordination motifs

Content Provider	Royal Society of Chemistry (RSC)
Author	Subramanian, Rohit H. Smith, Sarah J. Tezcan, F. Akif Radford, Robert J. Barnett, Brandon R. Figueroa, Joshua S.
Copyright Year	2016
Abstract	Given the prevalent role of α-helical motifs on protein surfaces in mediating protein–protein and protein–DNA interactions, there have been significant efforts to develop strategies to induce α-helicity in short, unstructured peptides to interrogate such interactions. Toward this goal, we have recently introduced hybrid metal coordination motifs (HCMs). HCMs combine a natural metal-binding amino acid side chain and a synthetic chelating group that are appropriately positioned in a peptide sequence to stabilize an α-helical conformation upon metal coordination. Here, we present a series of short peptides modified with HCMs consisting of a His and a phenanthroline group at i and i + 7 positions that can induce α-helicity in a metal-tunable fashion as well as direct the formation of discrete dimeric architectures for recognition of biological targets. We show that the induction of α-helicity can be further modulated by secondary sphere interactions between amino acids at the i + 4 position and the HCM. A frequently cited drawback of the use of peptides as therapeutics is their propensity to be quickly digested by proteases; here, we observe an enhancement of up to ∼100-fold in the half-lives of the metal-bound HCM-peptides in the presence of trypsin. Finally, we show that an HCM-bearing peptide sequence, which contains the DNA-recognition domain of a bZIP protein but is devoid of the obligate dimerization domain, can dimerize with the proper geometry and in an α-helical conformation to bind a cognate DNA sequence with high affinities (Kd ≥ 65 nM), again in a metal-tunable manner.
Starting Page	5453
Ending Page	5461
Page Count	9
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	7
Issue Number	8
Journal	Chemical Science
DOI	10.1039/c6sc00826g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Subscribed
Subject Keyword	Trypsin Carboxylic acid DNA Dissociation constant Phenanthroline Peptide Biomolecular structure Protein Molecular geometry
Content Type	Text
Resource Type	Article
Subject	Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Artificial protein sensors

Synthesis and properties of chemotactic peptide analogs

Chirally Switching Metal Coordination Environments in Designed Peptides

Coordination properties of Cu(II) and Ni(II) ions towards the C-terminal peptide fragment -TYTEHA- of histone H4

Hydrocarbon constrained peptides – understanding preorganisation and binding affinity

Peptide Bond Modification for Metal Coordination: 3. Metal-Binding Properties of Phosphorus-Based Pseudo-peptides

Peptide Bond Modification for Metal Coordination: 1. Metal-Binding Properties of Hydroxamate-Based Pseudo-Peptides

Peptide Bond Modification for Metal Coordination: 3. Metal-Binding Properties of Phosphorus-Based Pseudo-peptides

Development of Cobalt-Binding Peptide Chelate from Human Serum Albumin: Cobalt-Binding Properties and Stability

Tunable helicity, stability and DNA-binding properties of short peptides with hybrid metal coordination motifs

Similar Documents

Artificial protein sensors

Synthesis and properties of chemotactic peptide analogs

Chirally Switching Metal Coordination Environments in Designed Peptides

Coordination properties of Cu(II) and Ni(II) ions towards the C-terminal peptide fragment -TYTEHA- of histone H4

Hydrocarbon constrained peptides – understanding preorganisation and binding affinity

Peptide Bond Modification for Metal Coordination: 3. Metal-Binding Properties of Phosphorus-Based Pseudo-peptides

Peptide Bond Modification for Metal Coordination: 1. Metal-Binding Properties of Hydroxamate-Based Pseudo-Peptides

Peptide Bond Modification for Metal Coordination: 3. Metal-Binding Properties of Phosphorus-Based Pseudo-peptides

Development of Cobalt-Binding Peptide Chelate from Human Serum Albumin: Cobalt-Binding Properties and Stability

Tunable helicity, stability and DNA-binding properties of short peptides with hybrid metal coordination motifs