5616-84-2

Upstream product

• 27483-27-8 N-(benzyloxycarbonyl)-D-valylprolylsarcosine tert-butyl ester 
• 101644-79-5 α-tert-butyl N-(benzyloxycarbonyl)-N-methylglycinate 
• 5616-82-0 N-(benzyloxycarbonyl)prolylsarcosine tert-butyl ester 
• 63219-23-8 [Methyl-((S)-pyrrolidine-2-carbonyl)-amino]-acetic acid tert-butyl ester 
• 5616-81-9 sarcosine tert-butyl ester 
• 19728-63-3 N-benzyloxycarbonyl-L-treonine 
• 5616-83-1 H-D-Val-Pro-Sar-OBu^t 

Downstream Products

• 2478-48-0 <3-(benzyloxy)-4-methyl-2-nitrobenzoyl>-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone 

Relevant academic research and scientific papers

Toward the design of an RNA:DNA hybrid binding agent

One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA:DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.