[NMR paper] NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
Related ArticlesNMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
J Pept Sci. 2013 Jan;19(1):33-45
Authors: Rawat A, Kumar D
Abstract
Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(?) chemical shifts and three bond H(N) -H(?) coupling constants indicated that most of the residues of the peptide are populating the ?-helical region of the Ramachandran (?, ?) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (10(2) -10(3) s(-1) ), inferred by the multiple chemical shift assignments in the region Leu4-Leu12 and around Pro23 (for residues Gln20-Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self-association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The (15) N NMR-relaxation data revealed (i) the presence of slow (microsecond-to-millisecond) timescale dynamics in the N-terminal region (Cys1-Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond-to-picosecond) motions in the C-terminal arm. Put together, the various results suggested that (i) the flexible C-terminal of sCT (from Thr25-Thr31) is involved in identification of specific target receptors, (ii) whereas the N-terminal of sCT (from Cys1-Gln20) in solution - exhibiting significant amount of conformational plasticity and strong bias towards biologically active ?-helical structure - facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs.
Structure-Based Drug Design
Structure-Based Drug Design
http://www.spectroscopynow.com/common/images/thumbnails/no_img.gifThe 13th Structure-Based Drug Discovery conference will feature the development of in silico technology as well as experimental approaches useful for accurately predicting and modeling the structures of proteins in structure-based drug design efforts.
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05-22-2013 04:43 PM
Scientists move toward rational design of artificial proteins - R & D Magazine
Scientists move toward rational design of artificial proteins - R & D Magazine
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Scientists move toward rational design of artificial proteins
R & D Magazine
Less vulnerable to chemical or metabolic breakdown than proteins, peptoids are promising for diagnostics, pharmaceuticals, and as a platform to build bioinspired nanomaterials, as scientists can build and manipulate peptoids with great precision. But ...
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08-23-2012 03:46 AM
Systematic Study of Protein Detection Mechanism of Self-Assembling 19F NMR/MRI Nanoprobes toward Rational Design and Improved Sensitivity
Systematic Study of Protein Detection Mechanism of Self-Assembling 19F NMR/MRI Nanoprobes toward Rational Design and Improved Sensitivity
Yousuke Takaoka, Keishi Kiminami, Keigo Mizusawa, Kazuya Matsuo, Michiko Narazaki, Tetsuya Matsuda and Itaru Hamachi
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja203996c/aop/images/medium/ja-2011-03996c_0004.gif
Journal of the American Chemical Society
DOI: 10.1021/ja203996c
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/fqTSjFalrGg
Structural Features of Cytochromes P450 and Ligands that Affect Drug Metabolism as Re
Structural Features of Cytochromes P450 and Ligands that Affect Drug Metabolism as Revealed by X-ray Crystallography and NMR.
Structural Features of Cytochromes P450 and Ligands that Affect Drug Metabolism as Revealed by X-ray Crystallography and NMR.
Future Med Chem. 2010 Sep 1;2(9):1451-1468
Authors: Gay SC, Roberts AG, Halpert JR
Cytochromes P450 (P450s) play a major role in the clearance of drugs, toxins, and environmental pollutants. Additionally, metabolism by P450s can result in toxic or carcinogenic products. The metabolism of...
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11-26-2010 05:32 PM
[NMR paper] Structural investigations of a human calcitonin-derived carrier peptide in a membrane
Structural investigations of a human calcitonin-derived carrier peptide in a membrane environment by solid-state NMR.
Related Articles Structural investigations of a human calcitonin-derived carrier peptide in a membrane environment by solid-state NMR.
Biochemistry. 2004 Oct 5;43(39):12459-68
Authors: Wagner K, Beck-Sickinger AG, Huster D
Previous studies have shown that human calcitonin (hCT) and its C-terminal fragment hCT(9-32) translocate in nasal epithelium. Moreover, hCT(9-32) was used as a carrier to internalize efficiently the green...
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11-24-2010 10:01 PM
[NMR paper] The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061--fr
The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061--from the NMR tube to the clinic.
Related Articles The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061--from the NMR tube to the clinic.
Biopolymers. 2004;76(4):309-23
Authors: Tsantrizos YS
The virally encoded serine protease NS3/NS4A is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. Until very recently, the...
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11-24-2010 09:25 PM
[NMR paper] Structural characterization by NMR of the natively unfolded extracellular domain of b
Structural characterization by NMR of the natively unfolded extracellular domain of beta-dystroglycan: toward the identification of the binding epitope for alpha-dystroglycan.
Related Articles Structural characterization by NMR of the natively unfolded extracellular domain of beta-dystroglycan: toward the identification of the binding epitope for alpha-dystroglycan.
Biochemistry. 2003 Nov 25;42(46):13717-24
Authors: Bozzi M, Bianchi M, Sciandra F, Paci M, Giardina B, Brancaccio A, Cicero DO
Dystroglycan (DG) is an adhesion molecule playing a...