Reproductive and Developmental Biology

The Korean Society of Animal Reproduction (한국동물번식학회)
권호 표지

The Search of Pig Pheromonal Odorants for Biostimulation Control System Technologies: III. Comparative Molecular Field Analysis (CoMFA) on Binding Affinities between Ligands of 2-(Cyclohexyloxy) Tetrahydrofurane Derivatives and Porcine Odorant Binding Protein

생물학적 자극 통제 수단으로 활용하기 위한 돼지 페로몬성 냄새 물질의 탐색: III. 2-(Cyclohexyloxy) Tetrahydrofurane 유도체와 Porcine Odorant Binding Protein 사이의 결합 친화력에 관한 비교 분자장 분석

  • Sung Nack-Do (Division of Applied Biological Chemistry, The College of Agricultural & Life Sciences, Chung-Nam National University) ;
  • Park Chang-Sik (Research Center for Transgenic Cloned Pigs, Chung-Nam National University) ;
  • Jung Hoon-Sung (Division of Applied Biological Chemistry, The College of Agricultural & Life Sciences, Chung-Nam National University) ;
  • Seong Min-Kyu (Laboratory of Protein Synthesis, Peptron Inc.)
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 박창식 (충남대학교 형질전환복제돼지 연구센터) ;
  • 정훈성 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 성민규 ((주)펩트론 단백질 합성 연구실)
  • Published : 2006.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

To search of new porcine pheromonal odorants for biostimulation control system technologies to improve reproductive efficiency in livestock species, the comparative molecular field analysis (CoMFA) for binding affinity constant $(p(Od)_{50})$ between porcine odorant binding protein (pOBP) and ligands of odorant 2-(cyclohexyloxy) tetrahydrofurane derivatives as substrate molecule was conducted and discussed. In the optimized CoMFA model AIV with chirality $(C_1'(R),\;C_2(S))$ in substrate molecule and atom based fit alignment (A) of odorants, the statistical results showed the best predictability of the binding affinities $(p(Od)_{50})$ based on the LOO cross-validated value $r^2_{cv}.\;(q^2=0.886)$ and non-cross-validated conventional coefficient $(r^2_{ncv}.=0.984)$. the binding affinity constants exhibited a good correlation with steric (40.8%), electrostatic (14.6%) and hydrophobic (44.6%) factors of the substrate molecules. from the analytical results of the contour maps, which may give us some valuable informations to the modification of odorants for effective binding affinity.

생물학적 자극통제 수단으로 활용하기 위한 돼지 웅성 페르몬성 분자를 탐색하고자 일련의 냄새 분자로서 2-(cyclo-hexyloxy) tetrahydrofurane 유도체들의 정량적인 구조와 수용체인 porcine odorant binding protein (pOBP)간의 결합 친화력 상수$(p(Od)_{50})$에 대한 비교 분자장 분석(CoMFA)을 실행하였다. 가장 양호한 CoMFA 모델 AIV $(r^2_{cv}.(q^2)=0.886$ 및 $r^2_{ncv}.=0.984$)은 기질 분자 내 입체 중심(chiral center)의 절대 배열이 $C_1(R),C_2(S)$인 분자를 atom based fit 방법으로 배열하였을 경우의 standard field와 indicator field가 조합된 CoMFA장의 조건에서 유도되었다. 이 CoMFA 모델은 입체장 40.8% 정전기장 14.6%및 소수성장 44.6%가 결합 친화력 상수에 영향을 미치는 요소임을 나타내었다. 등고도의 분석 결과로부터 효과적인 결합 친화력 냄새 분자를 수식하는 데 몇 가지 가치 있는 정보를 얻을 수 있었다.

Keywords

References

  1. Abraham MH, Gola JMR, Cometto-Muniz JE, Cain WS (2002): A model for odour thresholds. Chem Senses 27:95-104 https://doi.org/10.1093/chemse/27.2.95
  2. Clark M, Cramer III, RD, Jones DM, Patterson DE, Simeroth PE (1990): Comparative molecular field analysis (CoMFA). 2. Toward its use with 3D-structural databases. Tetrahedron Comput Methodol 3:47-59 https://doi.org/10.1016/0898-5529(90)90120-W
  3. Cramer RD, Paterson DE, Bunce JD (1988): Comparative molecular field analysis (CoMFA), 1. Effect of shape on binding of steroids to carrier proteins. J Am Chern Soc 110:5959-5967 https://doi.org/10.1021/ja00226a005
  4. Dal Monte M, Centini M, Anselmi C, Pelosi P (1993): Binding of selected odorants to bovine and porcine odorant-binding proteins. Chem Sences 18: 713-721 https://doi.org/10.1093/chemse/18.6.713
  5. Gower, DB, Hancock, MR (1982): In; Olfaction and Endocrine Regulation, W. Breipohl(Ed), IRL. Press, London, UK, pp 267-277
  6. Herent MF, Collin S, Pelosi P (1995): Affinities of nutty and green-smelling pyrazines and thiazoles to odorant-binding proteins, in relation with their lipophilicity. Chem Senses 20:601-608 https://doi.org/10.1093/chemse/20.6.601
  7. Kansy M (1996): Molecular properties, In; StructureProperty Correlations in Drug Research, H.V.D. Waterbeemed( Ed). Academic Press, Landers, RG. Co., Austin. Ch. 2
  8. Kellogg GE, Semus SF, Abraham DJ (1991): HINT: A new method of empirical field calculation for CoMFA. J Comp Aided Mol Design 5:545-552 https://doi.org/10.1007/BF00135313
  9. Kerr R (1994): Parallel helix bundles and ion channels: Molecular modeling via simulated and restrained molecular dynamics. Biophus J 67:1501-1515 https://doi.org/10.1016/S0006-3495(94)80624-1
  10. Krzymowski T, Grzegorzewski W, Stefanczyk-Krzymowska S, Skipor J, Wasowska B (1999): Humoral pathway for transfer of the boar pheromone, androstenol from the nasal mucosa to the brain and hypophysis of gilts. Theriogenology 52:1225-1240 https://doi.org/10.1016/S0093-691X(99)00200-9
  11. Kubinyi H (1993): 3D QSAR Drug Design, Theory, Methods and Applications, ESCOM. Leiden
  12. Marshall GR, Barry CD, Bosshard HE, Dammkoehler RA, Dunn DA (1979): The conformational parameter in drug design: Active analog approach. In; Computer-assisted drug design., E.C. Olsen and RE. Christoffersen(Eds), American Chemical Society, Washington, D.C. pp 205-226
  13. PBS: The leader in animal health & nutrition, PBS Animal Health, PO Box 9101, Canton, Ohio 447119101. U.S.A
  14. Pelosi P, Tirindelli R (1989): Structure/Activity Studies and Characterization of an Odorant-Binding Protein. Chemical Senses, Vol. 1. In; Receptor events and transduction in taste and olfaction., J.G. Brand, J.H. Teeter, R.H. Cagon and M.R. Kare(Eds), Marel Dekker, New York., pp 207-226
  15. Pevsner J, Hou V, Snowman AM, Snyder SH (1990): Odorant-binding protein, characterization of ligand binding. J BioI Chem 265:6118-6125
  16. Rekwot PI, Ogwu D, Oyedipe EO, Sekoni VO (2001): The role of pheromones and biostimulation in animal reproduction. Anim Reprod Sci 65:157-170 https://doi.org/10.1016/S0378-4320(00)00223-2
  17. Shrestha NP, Edwards S, English PR, Robertson JF (2001): An evaluation of boar pheromone spray to aid the stimulation and detection of estrus in small farms in Nepal. Asian-Aust J Anim Sci 14:697-700 https://doi.org/10.5713/ajas.2001.697
  18. Spinelli S, Vincent F, Pelosi P, Tegoni M, Cambillau C (2002): Boar salivar lipocalin: Three-dimensional X-ray structure and androstenol/androstenone docking simulations. Eur J Biochem 269:2449-2456 https://doi.org/10.1046/j.1432-1033.2002.02901.x
  19. Stahle L, Wold S (1988): Multivariate data analysis and experimental design in biomedical research. Prog Med Chem 25:292-334
  20. Sung ND (2002): Development of new agrochemicals by quantitative structure-activity relationship (QSAR) methodology. II. The linear free energy relationship (LFER) ang descriptors. Kor J Pesticide Sci 6:231-243
  21. Sung ND, Kim CH, Jin DI, Park CS (2004): The search of pig pheromonal odorants for biostimulation control system technologies: I. Ligand based molecular shape similarity of 5a-androst-16-en-3one analogous and their physico-chemical parameters. Reprod Dev BioI 28:45-52
  22. Sung ND, Park CS, Choi YS, Myung PK (2005): The search of pig pheromonal odorants for biostimulation control system technologies: II. Holographic QSAR model for binding affinities between ligands of volatile odorants molecules and porcine odorant binding protein (POBP). Reprod Dev BioI 29:43-48
  23. SYBYL, Tripos Associates, Inc., 1699 S. Hanley Rd., Suite 303, St. Louis, MO. 63144-2913, U.S.A
  24. Vincent F, Spinelli S, Ramoni R, Grolli S, Pelosi P, Cambillau C, Tegon M (2000): Complexes of porcine odorant binding protein with odorant molecules belonging to different chemical classes. J Mol BioI 300:127-139 https://doi.org/10.1006/jmbi.2000.3820