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阳离子胸腺嘧啶脱氧核糖胍与RNA同聚核苷酸的结合研究。

Binding studies of cationic thymidyl deoxyribonucleic guanidine to RNA homopolynucleotides.

作者信息

Browne K A, Dempcy R O, Bruice T C

机构信息

Department of Chemistry, University of California, Santa Barbara 93106, USA.

出版信息

Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7051-5. doi: 10.1073/pnas.92.15.7051.

DOI:10.1073/pnas.92.15.7051
PMID:7542784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC41469/
Abstract

Deoxyribonucleic guanidine is a potential antisense agent that is generated via the replacement of the negative phosphodiester linkages of DNA [--O--(PO2-)--O--] with positively-charged guanidinium (g) linkages [--NH--C(==NH2+)--NH--]. A pentameric thymidyl deoxyribonucleic guanidine molecule [d(Tg)4T-azido] has been shown to base pair specifically to poly(rA) with an unprecedented affinity. Both double and triple strands consisting of one and two equivalents of d(Tg)4T-azido paired with one equivalent of poly(rA) are indicated by thermal denaturation experiments. At an ionic strength of 0.22, the five bases of d(Tg)4T-azido are estimated to dissociate from a double helix with poly(rA) at > 100 degrees C! The effect of ionic strength on thermal denaturation is very pronounced, with stability greatest at low ionic strengths. The method of continuous variation indicates that there is an equilibrium complex with a molar ratio of d(Tg) to r(Ap) or d(Ap) of 2:1. Based on this evidence, models of the structures of d(Tg)9T-azido bound to r(Ap)9A are proposed.

摘要

脱氧核糖核酸胍是一种潜在的反义剂，它是通过用带正电荷的胍鎓（g）键[--NH--C(==NH2+)--NH--]取代DNA的负磷酸二酯键[--O--(PO2-)--O--]而产生的。已证明一种五聚体胸苷脱氧核糖核酸胍分子[d(Tg)4T-叠氮化物]能以前所未有的亲和力与聚（rA）特异性碱基配对。热变性实验表明，由一当量和两当量的d(Tg)4T-叠氮化物与一当量的聚（rA）组成的双链和三链均存在。在离子强度为0.22时，估计d(Tg)4T-叠氮化物的五个碱基在高于100℃时会从与聚（rA）的双螺旋中解离！离子强度对热变性的影响非常显著，在低离子强度下稳定性最大。连续变化法表明存在一种平衡复合物，其d(Tg)与r(Ap)或d(Ap)的摩尔比为2:1。基于这一证据，提出了与r(Ap)9A结合的d(Tg)9T-叠氮化物的结构模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/41469/3cb3784e87f8/pnas01491-0410-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/41469/73cb78121086/pnas01491-0410-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/41469/3cb3784e87f8/pnas01491-0410-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/41469/73cb78121086/pnas01491-0410-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/41469/3cb3784e87f8/pnas01491-0410-b.jpg

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