Reproductive and Developmental Biology

The Korean Society of Animal Reproduction (한국동물번식학회)
권호 표지

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)

생물학적 자극 통제 수단으로 활용하기 위한 돼지 페로몬성 냄새 물질의 탐색: Ⅱ. 휘발성 냄새분자의 리간드와 Porcine Odorant Binding Protein (pOBP) 사이의 결합 친화력에 관한 홀로그래피적 QSAR 모델

  • Sung N. D. (College of Agricultural & Life Sciences, Division of Applied Biological Chemistry, Chungnam National University) ;
  • Park C. S. (Division of Animal Science and Resources, Research Center for Transgenic Cloned Pig, Chungnam National University) ;
  • Choi Y. S. (Division of Animal Science and Resources, Chungnam National University) ;
  • Myung P. K. (Division of Pharmacy, College of Pharmacy, Chungnam National University)
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 박창식 (충남대학교 동물자원학부, 형질전환복제돼지연구센터) ;
  • 최양석 (충남대학교 동물자원학부) ;
  • 명평근 (충남대학교 약학대학 약학부)
  • Published : 2005.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

To search of a new porcine pheromonal odorants for biostimulation control system technologies to offer a potentially useful and practical way to improve reproductive efficiency in livestock species, the holographic quantitative structure activity relationship (HQSAR) model between odorants, 2-phenoxytetrahydrofurane (A), 2-cyclohexyl-oxytetrahydrofurane (B), derivatives and binding affinity constants (p[Od.]/sub 50/) for porcine odorant-binding protein (pOBP) as receptor of pig pheromones were derivated and disscused. The binding affinity constants of cyclohexyl substituents (A) for pOBP were higher (A>B) than that of phenyl substituents (B). It was revealed that the optimum HQSAR model XI using PLS analyses had a fragment length (5∼8) with chirality at 5 components and hologram length 97 bin, which had a cross-validated q²(predictablities) of 0.916, and a conventional correlation coefficient r² (fitness) of 0.988, respectively. From the atomic contribution, the C3 and C5 atom in 2-oxyfuryl group contributed to binding affinity constants, whereas the central carbon atom in tert-butyl group on the cyclohexyl ring and the C4 atom of furyl group parts showed no contribution.

돼지 웅성 페르몬인 5a-androst-16-en-3-one을 대체할 수 있는 활성 분자를 탐색하여 가축의 생산과 수요를 조절하기 위한 생물학적 자극 통제 수단으로 활용하고자 냄새 분자로서 2-cyclohexyloxytetrahydrofurane (A) 및 2-phenoxytetrahydrofurane (B) 유도체들의 구조 변화와 수용체인 porcine odorant binding protein (pOBP)에 대한 결합친화력 상수(p[Od.]/sub 50/) 사이의 정량적인 구조-활성관계에 관한 분자 HQSAR 모델XI을 유도하였다. 냄새 분자 중에서 cyclohexyl-치환체(A)가 phenyl-치환체(B)보다 높은 결합 친화력을 나타내었으며(A>B) 모델XI은 분자 조각크기(5∼8), 홀로그램 길이(97 bin)의 키랄성(chirality)조건에서 예측성(q²=0.916)과 상관성(r²=0.988)이 매우 양호하였다. 기여도(contribution map)로부터 냄새 분자의 결합 친화력 상수에 기여하는 부분은 2-oxyfuryl group의 C3 및 C5 원자인 반면에 cyclohexyl 고리상 tert-butyl group의 중심 탄소 원자와 furyl group의 C4 원자 부분은 기여하지 않았다.

Keywords

References

  1. Buck LB (2004): The search for odorant receptors. Commentary. Cell 116:5117-5119
  2. Cutforth T, Moring L, Mendelsohn M, Nemes A, Shah NM, Kim MM, Frisen J, Axel R (2003): Axonal ephrin-As and odorant receptors: Coordinate determination of the olfactory sensory map. Cell 114: 311-322 https://doi.org/10.1016/S0092-8674(03)00568-3
  3. 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
  4. Felicioli A, Ferraro F, Ganni M, Garibotti M, Navarrini A, Pes D, Pelosi P (1994): Odorant-binding proteins and biosensors for odours, Life Chem Rep 11:347-355
  5. Gower DB, Hancock MR (1982): In; Olfaction and Endocrine Regulation (Breipohl, W. ed.) IRL. Press, London 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. Heritage TW, Lowis DR (1999): Molecular hologram QSAR. Ch. 4., In Rational Drug Design. ACS Symposium Series 719, American Chemical Society, Washington, DC
  8. Kubinyi H (1993a): QSAR, Hansch analysis and related approaches, In Methods and Principles in Medicinal Chemistry (ed. Mannhold, R., Krogsgaard, LP and Timmerman, H), Vol 1, VCH, Weinheim
  9. Kubinyi H (1993b): 3D-QSAR in Drug Design; Theory, Methods and Applications. ESCOM, Leiden
  10. Lowis DR (1997): HQSAR. A new, highly prediction QSAR technique. Tripos Technical Notes, Vol 1, No. 5
  11. Meyer AY, Richard WG (1991): Similarity of molecular shape. J Comput Aided Mol Design 5:427-439 https://doi.org/10.1007/BF00125663
  12. Pevsner J, Hou V, Snowman AM, Snyder SH (1990): Odorant-binding protein, charaterization of ligand binding. J Biol Chem 265:6118-6125
  13. Reddy MR, Parrill AL (1999): Overview of rational drug design. In Rational Drug Design. Ch. 1., ACS Symposium Series 719, American Chemical Society, Washington, DC
  14. Rekwot PI, Ogwu D, Oyedipe EO, Sekoni VO (2001): The role of pheromones and biostimulation in anima1 reproduction. Animal Reproduction Science 65:157-170 https://doi.org/10.1016/S0378-4320(00)00223-2
  15. Rossiter KJ (1996): Structure-odor relationships. Chem Rev 96:3201-1300 https://doi.org/10.1021/cr950068a
  16. 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
  17. Shykind BM, Rohani SC, O'Donnell S, Nemes A, Mendelsohn M, Sun Y, Axel R Barnea G (2004): Gene switching and stability of odorant receptor gene choice. Cell 117:801-815 https://doi.org/10.1016/j.cell.2004.05.015
  18. Sung ND, Park CS, You JW, Jang SC, Lee MJ (2004a): Prediction of odor recognition from the two-dimensional quantitative structure-activity relationship between volatile odorant molecules and bovine odorant binding proteins. Proceedings of annual meeting on new wave in microbiology, Autumn. The Korean Society for Applied Biological Chemistry pp 169
  19. Sung ND, Kim CH, Jin DI, Park CS (2004b): The search of pig pheromonal ordorants for biostimulation control system technologies: I. Ligand based molecular shape similarity of 5$\alpha$-androst-16- en-3-one analogous and their physico-chemical parameters. Reprod Dev Biol 28:45-52
  20. Sybyl (Ver. 6.92), Tripos Associates, Inc., 1699 S. Hanley Rd., Suite 303, St. Louis, MO. 63144-2913, U. S. A. http://www.tripos.com/Bookshelf/qsar/
  21. 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 Biol 300:127-139 https://doi.org/10.1006/jmbi.2000.3820
  22. Wold S, Dunn III WJ (1983): Multivariate quantitative structure activity relationships (QSAR): Conditions for thier applicability. J Chem Inf Comput Sci 23:6-13 https://doi.org/10.1021/ci00037a002