Random Articles
Reseach Article
Virtual Screening of Dipeptidyl Peptidase IV Inhibitors from Zinc Database
| International Journal of Computer Applications |
| Foundation of Computer Science (FCS), NY, USA |
| Volume 56 - Number 8 |
| Year of Publication: 2012 |
| Authors: Phani Kumar Yadla, Allam Appa Rao, A. Swaroopa Rani, M. Naresh Babu |
10.5120/8912-2959
|
Phani Kumar Yadla, Allam Appa Rao, A. Swaroopa Rani, M. Naresh Babu . Virtual Screening of Dipeptidyl Peptidase IV Inhibitors from Zinc Database. International Journal of Computer Applications. 56, 8 ( October 2012), 31-34. DOI=10.5120/8912-2959
Abstract
Dipeptidyl peptidase IV (DPP IV) is a serine exopeptidase that cleaves X-proline dipeptides from the N terminus of polypeptides. Dipeptidyl peptidase IV enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP). Hence, DPP IV has an important role in glucose homeostasis, and was established as a potential target for therapy in type II diabetes. Hence, there is a need to identify the most potent compound that would specifically target DPP IV. Initially, protein structure DPP IV was extracted from Protein Data Bank by performing a search resulted in 86 hits. They are filtered based on the presence of X-ray diffraction as the experimental method, between 2. 0 and 2. 5 Aº resolution and with bound ligands. From the result, presence of breaks in the protein are checked and based on Ramchandran plot, 2QOE was selected as the protein target. Further analysis was carried to screen compounds from ZINC database, on Lipinski's rule of 5 using the virtual screening software like eHiTS.
References
- Barnett A (November 2006). "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". Int. J. Clin. Pract. 60 (11): 1454–70. doi:10. 1111/j. 1742-1241. 2006. 01178. x. PMID 17073841
- Gupta R, Walunj SS, Tokala RK (2009) Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 10: 71-87
- Orsakov, C. Diabetologia 1992, 35, 701.
- The crystal structure of dipeptidyl peptidase iv (cd26) reveals its functional regulation and enzymatic mechanism , http://www. pnas. org/cgi/content/abstract/0230620100v1
- Dipeptidyl peptidase iv and related enzymes in cell biology and liver disorders . gorrellmd. www. clinsci. org/cs/108/0277/cs1080277. html
- Wilhelm A. Weihofen , Jiango Liu, Werner Reutter, Wolfram Saenger Crystal Structure of CD26/Dipeptidyl-peptidase IV in Complex with Adenosine Deaminase Reveals a Highly Amphiphilic Interface , J. Biol. Chem. , Vol. 279, Issue 41, 43330-43335, October 8, 2004.
- Engel, M. ; Hoffmann, T. ; Wagner, L. ; Wermann, M. ; Heiser, U. ; Kiefersauer, R. ; Huber, R. ; Bode, W. ; Demuth, H. -U. ; Brandstetter,H ,Proc. Nat. Acad. Sci. 100: 5063-5068, 2003.
- Kenton L. Longenecker,Kent D. Stewart,David J. Madar,Clarissa G. Jakob,Elizabeth H. Fry, Sherwin Wilk, Chun W. Lin,Stephen J. Ballaron,Michael A. Stashko,Thomas H. Lubben,Hong Yong, Daisy Pireh,Zhonghua Pei,Fatima Basha,Paul E. Wiedeman,Thomas W. von Geldern, James M. Trevillyan andVincent S. Stoll; Biochemistry,45 (24), 7474 -7482, 2006.
- Holst JJ, Deacon CF (2005) Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia DOI 10. 1007/S00125-005-1705-7.
- Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ (2001) Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609–613.
- Kieffer TJ, McIntosh CH, Pederson RA (1995) Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136:3585–3596.
- Knudsen LB, Pridal L (1996) Glucagon-like peptide-1-(9–36) amide is a major metabolite of glucagon-like peptide-1-(7–36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor. Eur J Pharmacol 318:429–435.
- Gault VA, Parker JC, Harriott P, Flatt PR, O Harte FP (2002) Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide, GIP(3–42), is a GIP receptor antagonist in vivo. J Endocrinol 175:525–533.
- Ludwig A, Schiemann F, Mentlein R, Lindner B, Brandt E (2002) Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine. J LeukocBiol 72:183–191.
- Proost P, Schutyser E, Menten P et al (2001) Amino-terminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, while preserving antiangiogenic properties. Blood 98:3554–3561.
Index Terms
Keywords