دورية أكاديمية
أعرض في EDS

Papain-Mediated Conjugation of Peptide Nucleic Acids to Delivery Peptides: A Density Functional Theory/Molecular Mechanics Metadynamics Study in Aqueous and Organic Solvent.

التفاصيل البيبلوغرافية
العنوان: Papain-Mediated Conjugation of Peptide Nucleic Acids to Delivery Peptides: A Density Functional Theory/Molecular Mechanics Metadynamics Study in Aqueous and Organic Solvent.
المؤلفون: González RD; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal.; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra 3004-504, Portugal.; Institute for Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, Coimbra 3030-789, Portugal., Carvalho ATP; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal.; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra 3004-504, Portugal.; Almac Sciences, Department of Biocatalysis and Isotope Chemistry, Almac House, 20 Seagoe Industrial Estate ,Craigavon, Northern Ireland BT63 5QD, United Kingdom.
المصدر: The journal of physical chemistry. B [J Phys Chem B] 2024 Aug 08; Vol. 128 (31), pp. 7500-7512. Date of Electronic Publication: 2024 Jul 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101157530 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5207 (Electronic) Linking ISSN: 15205207 NLM ISO Abbreviation: J Phys Chem B Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c1997-
مواضيع طبية MeSH: Peptide Nucleic Acids*/chemistry , Papain*/chemistry , Papain*/metabolism , Water*/chemistry , Solvents*/chemistry , Peptides*/chemistry , Density Functional Theory*, Molecular Dynamics Simulation
مستخلص: Enzymatic peptide synthesis is a powerful alternative to solid-phase methods, as enzymes can have high regio- and stereoselectivity and high yield and require mild reaction conditions. This is beneficial in formulation research due to the rise of nucleic acid therapies. Peptide nucleic acids (PNAs) have a high affinity toward DNA and RNA, and their solubility and cellular delivery can be improved via conjugation to peptides. Here, we designed and assessed the viability of the papain enzyme to conjugate four PNA-peptide models in water and an organic solvent using QM/MM metadynamics. We found that the reactions in water yield better results, where three conjugates could potentially be synthesized by the enzyme, with the first transition state as the rate-limiting step, with an associated energy of 14.53 kcal mol -1 , although with a slight endergonic profile. The results highlight the importance of considering the enzyme pockets and different substrate acceptivities and contribute to developing greener, direct, and precise synthetic routes for nucleic acid-based therapies. By exploring the enzyme's potential in conjunction with chemical synthesis, current protocols can be simplified for the synthesis of longer nucleic acids and peptide sequences (and, by extension, proteins) from smaller oligo or peptide blocks.
References: Artif DNA PNA XNA. 2011 Jul-Dec;2(3):90-9. (PMID: 22567192)
Biomol Concepts. 2013 Jun;4(3):287-308. (PMID: 25436581)
Org Lett. 2007 Aug 16;9(17):3291-3. (PMID: 17661472)
Nat Protoc. 2007;2(12):3247-56. (PMID: 18079725)
Bioorg Med Chem Lett. 2017 Aug 1;27(15):3337-3341. (PMID: 28610975)
Biochemistry. 1967 Apr;6(4):1047-53. (PMID: 6032452)
Biochemistry. 2005 Jan 11;44(1):138-48. (PMID: 15628854)
Curr Pharm Biotechnol. 2014;15(3):210-9. (PMID: 24938896)
J Chem Phys. 2007 Jan 7;126(1):014101. (PMID: 17212484)
Biochemistry. 2008 Feb 19;47(7):2025-35. (PMID: 18225918)
Proc Natl Acad Sci U S A. 2019 Jun 11;116(24):11737-11746. (PMID: 31123145)
Protein Sci. 2018 Jan;27(1):293-315. (PMID: 29067766)
Macromol Biosci. 2017 Nov;17(11):. (PMID: 28722358)
Biochem J. 1969 Apr;112(3):343-55. (PMID: 4979349)
Int J Mol Sci. 2020 Apr 06;21(7):. (PMID: 32268473)
Protein Sci. 2016 Jan;25(1):295-301. (PMID: 26103917)
Biochemistry. 1967 Dec;6(12):3711-7. (PMID: 6076621)
Protein Eng. 1995 Oct;8(10):1039-47. (PMID: 8771185)
J Comput Aided Mol Des. 2017 Jan;31(1):147-161. (PMID: 27787702)
J Comput Chem. 2009 Dec;30(16):2785-91. (PMID: 19399780)
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713. (PMID: 26574453)
J Am Chem Soc. 2007 Nov 7;129(44):13633-45. (PMID: 17935329)
Eur J Hum Genet. 2004 Sep;12(9):694-700. (PMID: 15213706)
Mol Pharm. 2023 Dec 4;20(12):6079-6089. (PMID: 37941379)
Mol Cells. 2009 Oct 31;28(4):341-5. (PMID: 19812898)
J Biol Chem. 1995 Jul 14;270(28):16645-52. (PMID: 7622473)
J Org Chem. 2007 May 11;72(10):3909-12. (PMID: 17432905)
Bioconjug Chem. 1991 Jan-Feb;2(1):1-12. (PMID: 1878406)
J Theor Biol. 2001 Apr 21;209(4):417-29. (PMID: 11319891)
Acta Crystallogr B. 1992 Feb 1;48 ( Pt 1):67-75. (PMID: 1616693)
Phys Chem Chem Phys. 2016 Dec 7;18(48):32847-32861. (PMID: 27883128)
Pharmaceutics. 2020 Mar 03;12(3):. (PMID: 32138146)
Org Lett. 2020 Jan 17;22(2):533-536. (PMID: 31904984)
ACS Chem Biol. 2019 Jun 21;14(6):1280-1292. (PMID: 31063345)
Nat Rev Drug Discov. 2020 Oct;19(10):673-694. (PMID: 32782413)
Biochemistry. 2013 Jul 30;52(30):5145-54. (PMID: 23862626)
Proteins. 2006 Nov 15;65(3):712-25. (PMID: 16981200)
Polymers (Basel). 2016 May 13;8(5):. (PMID: 30979286)
Phys Rev E Stat Nonlin Soft Matter Phys. 2010 May;81(5 Pt 2):055701. (PMID: 20866290)
Front Chem. 2017 Oct 17;5:81. (PMID: 29094037)
J Chem Phys. 2020 May 21;152(19):194103. (PMID: 33687235)
J Chem Theory Comput. 2010 Aug 10;6(8):2348-64. (PMID: 26613491)
Sci Rep. 2018 Feb 13;8(1):2950. (PMID: 29440726)
Biochemistry. 2014 Sep 23;53(37):5930-46. (PMID: 25196915)
Nucleic Acids Res. 2002 Feb 15;30(4):950-7. (PMID: 11842106)
المشرفين على المادة: 0 (Peptide Nucleic Acids)
EC 3.4.22.2 (Papain)
059QF0KO0R (Water)
0 (Solvents)
0 (Peptides)
تواريخ الأحداث: Date Created: 20240725 Date Completed: 20240808 Latest Revision: 20240814
رمز التحديث: 20240814
مُعرف محوري في PubMed: PMC11317979
DOI: 10.1021/acs.jpcb.4c02294
PMID: 39052428
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5207
DOI:10.1021/acs.jpcb.4c02294