Amino acids of the adamantane series. I. Synthesis and antiviral activity of α-amino acids of the adamantane series and their derivatives

1985 ◽  
Vol 19 (7) ◽  
pp. 474-478
Author(s):  
P. A. Krasutskii ◽  
I. G. Semenova ◽  
M. I. Novikova ◽  
A. G. Yurchenko ◽  
N. A. Leont'eva ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Adamantane Series

ChemInform Abstract: Amino Acids of the Adamantane Series. Part 2. Synthesis of AdamantylSubstituted Amino Alcohols from α-Amino Acids and Their Antiviral Activity.

ChemInform ◽  
1988 ◽  
Vol 19 (9) ◽  
Author(s):  
P. A. KRASUTSKII ◽  
I. G. SEMENOVA ◽  
M. I. NOVIKOVA ◽  
A. G. YURCHENKO ◽  
N. A. LEONT'EVA ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Amino Alcohols ◽  
Adamantane Series

Amino acids of the adamantane series II. Synthesis of adamantyl-containing amino alcohols from ?-amino acids and their antiviral activity

1987 ◽  
Vol 21 (7) ◽  
pp. 512-515 ◽  
Author(s):  
P. A. Krasutskii ◽  
I. G. Semenova ◽  
M. I. Novikova ◽  
A. G. Yurchenko ◽  
N. A. Leont'eva ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Amino Alcohols ◽  
Adamantane Series

ChemInform Abstract: Amino Acids of the Adamantane Series. Part l. Synthesis and Antiviral Activity of Adamantane a-Aminoacids and Their Derivatives.

1986 ◽  
Vol 17 (2) ◽  
Author(s):  
P. A. KRASUTSKII ◽  
I. G. SEMENOVA ◽  
M. I. NOVIKOVA ◽  
A. G. YURCHENKO ◽  
N. A. LEONTIEVA ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Adamantane Series

ChemInform Abstract: α-Amino Acids of the Adamantane Series. Part 3. Deamination as a Way of Synthesis of Homoadamantane Derivatives.

ChemInform ◽  
1990 ◽  
Vol 21 (17) ◽  
Author(s):  
P. A. KRASUTSKII ◽  
I. G. SEMENOVA ◽  
E. E. SAFRONOVA ◽  
M. I. NOVIKOVA ◽  
A. G. YURCHENKO
Keyword(s):  
Amino Acids ◽  
Adamantane Series

ChemInform Abstract: Synthesis of Unsaturated Carboxylic and Amino Acids of Adamantane Series with the Use of Organophosphorus Reagents.

ChemInform ◽  
2010 ◽  
Vol 33 (42) ◽  
pp. no-no
Author(s):  
N. I. Miryan ◽  
S. D. Isaev ◽  
A. G. Yurchenko ◽  
I. V. Gulyaiko ◽  
T. Yu. Voinovskaya ◽  
...  
Keyword(s):  
Amino Acids ◽  
Adamantane Series

Mixed compounds of nickel (II) with amino acids and ethylenediamine and their antiviral activity

1990 ◽  
Vol 24 (8) ◽  
pp. 573-576
Author(s):  
A. E. Shvelashvili ◽  
E. I. Boreko ◽  
G. V. Vladyko ◽  
L. V. Korobchenko ◽  
M. V. Karkarashvili ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antiviral Activity

Small Molecules that Mimic Components of Bioactive Protein Surfaces

2004 ◽  
Vol 57 (9) ◽  
pp. 855 ◽  
Author(s):  
David P. Fairlie
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Small Molecules ◽  
G Protein ◽  
Selective Inhibition ◽  
Structural Components ◽  
Protein Surfaces ◽  
Biological Responses ◽  
Anti Inflammatory ◽  
G Protein Coupled

Small molecules designed to mimic specific structural components of a protein (peptide strands, sheets, turns, helices, or amino acids) can be expected to display agonist or antagonist biological responses by virtue of interacting with the same receptors that recognize the protein. Here we describe some minimalist approaches to structural mimetics of amino acids and of strand, turn, or helix segments of proteins. The designed molecules show potent and selective inhibition of protease, transferase, and phospholipase enzymes, or antagonism of G-protein coupled or transcriptional receptors, and have potent anti-tumour, anti-inflammatory, or antiviral activity.

scholarly journals Mutational analysis of Aedes aegypti Dicer 2 provides insights into the biogenesis of antiviral exogenous small interfering RNAs

2022 ◽  
Vol 18 (1) ◽  
pp. e1010202
Author(s):  
Rommel J. Gestuveo ◽  
Rhys Parry ◽  
Laura B. Dickson ◽  
Sebastian Lequime ◽  
Vattipally B. Sreenu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Aedes Aegypti ◽  
Semliki Forest Virus ◽  
Mutational Analysis ◽  
Helicase Domain ◽  
Small Interfering Rnas ◽  
Rnase Iii ◽  
Argonaute 2 ◽  
Sirna Pathway

The exogenous small interfering RNA (exo-siRNA) pathway is a key antiviral mechanism in the Aedes aegypti mosquito, a widely distributed vector of human-pathogenic arboviruses. This pathway is induced by virus-derived double-stranded RNAs (dsRNA) that are cleaved by the ribonuclease Dicer 2 (Dcr2) into predominantly 21 nucleotide (nt) virus-derived small interfering RNAs (vsiRNAs). These vsiRNAs are used by the effector protein Argonaute 2 within the RNA-induced silencing complex to cleave target viral RNA. Dcr2 contains several domains crucial for its activities, including helicase and RNase III domains. In Drosophila melanogaster Dcr2, the helicase domain has been associated with binding to dsRNA with blunt-ended termini and a processive siRNA production mechanism, while the platform-PAZ domains bind dsRNA with 3’ overhangs and subsequent distributive siRNA production. Here we analyzed the contributions of the helicase and RNase III domains in Ae. aegypti Dcr2 to antiviral activity and to the exo-siRNA pathway. Conserved amino acids in the helicase and RNase III domains were identified to investigate Dcr2 antiviral activity in an Ae. aegypti-derived Dcr2 knockout cell line by reporter assays and infection with mosquito-borne Semliki Forest virus (Togaviridae, Alphavirus). Functionally relevant amino acids were found to be conserved in haplotype Dcr2 sequences from field-derived Ae. aegypti across different continents. The helicase and RNase III domains were critical for silencing activity and 21 nt vsiRNA production, with RNase III domain activity alone determined to be insufficient for antiviral activity. Analysis of 21 nt vsiRNA sequences (produced by functional Dcr2) to assess the distribution and phasing along the viral genome revealed diverse yet highly consistent vsiRNA pools, with predominantly short or long sequence overlaps including 19 nt overlaps (the latter representing most likely true Dcr2 cleavage products). Combined with the importance of the Dcr2 helicase domain, this suggests that the majority of 21 nt vsiRNAs originate by processive cleavage. This study sheds new light on Ae. aegypti Dcr2 functions and properties in this important arbovirus vector species.

Quantum-Chemical Investigations of 5-Bromo-2'-Deoxyuridine Derivatives with Antiviral Activity

2006 ◽  
Vol 71 (5) ◽  
pp. 691-697
Author(s):  
Zhivko A. Velkov ◽  
Yasen Zh. Velkov ◽  
Alia V. Tadjer ◽  
Ivanka G. Stankova
Keyword(s):  
Amino Acids ◽  
Antiviral Activity ◽  
Quantum Chemical Calculations ◽  
Quantum Chemical ◽  
Molecular Descriptors ◽  
Structure Investigation ◽  
Determining Factor ◽  
Semiempirical Quantum Chemical Calculations

The article describes the results of semiempirical quantum-chemical calculations for a series of 3',5'-esters of 5-bromo-2'-deoxyuridine with amino acids or peptides. These compounds were synthesized and tested for antiviral activity as potential prodrugs of the parent 5-bromonucleoside. It was not clear why only some of the compounds were active. On the basis of structure investigation and the calculated molecular descriptors, it was found that the determining factor for obtaining appropriate prodrugs of 5-bromo-2'-deoxyuridine is the lipophilicity of the esters.

scholarly journals Flexibility in Nucleic Acid Binding Is Central to APOBEC3H Antiviral Activity

2019 ◽  
Vol 93 (24) ◽  
Author(s):  
Jennifer A. Bohn ◽  
Justin DaSilva ◽  
Siarhei Kharytonchyk ◽  
Maria Mercedes ◽  
Jennifer Vosters ◽  
...  
Keyword(s):  
Amino Acids ◽  
Nucleic Acid ◽  
Antiviral Activity ◽  
Reverse Transcription ◽  
Rna Binding ◽  
Viral Dna ◽  
Dna Substrates ◽  
Apobec3 Proteins ◽  
Rna Interaction ◽  
Hiv 1

ABSTRACT APOBEC3 proteins APOBEC3F (A3F), APOBEC3G (A3G), and APOBEC3H (A3H) are host restriction factors that inhibit HIV-1 through DNA cytidine deaminase-dependent and -independent mechanisms and have either one (A3H) or two (A3F and A3G) zinc-binding domains. A3H antiviral activity encompasses multiple molecular functions, all of which depend on recognition of RNA or DNA. A3H crystal structures revealed an unusual interaction with RNA wherein an RNA duplex mediates dimerization of two A3H proteins. In this study, we sought to determine the importance of RNA-binding amino acids in the antiviral and biochemical properties of A3H. We show that the wild-type A3H-RNA interaction is essential for A3H antiviral activity and for two deaminase-independent processes: encapsidation into viral particles and inhibition of reverse transcription. Furthermore, an extensive mutagenesis campaign revealed distinct roles for two groups of amino acids at the RNA binding interface. C-terminal helix residues exclusively bind RNA, and loop 1 residues play a dual role in recognition of DNA substrates and in RNA binding. Weakening the interface between A3H and RNA allows DNA substrates to bind with greater affinity and enhances deamination rates, suggesting that RNA binding must be disrupted to accommodate DNA. Intriguingly, we demonstrate that A3H can deaminate overhanging DNA strands of RNA/DNA heteroduplexes, which are early intermediates during reverse transcription and may represent natural A3H substrates. Overall, we present a mechanistic model of A3H restriction and a step-by-step elucidation of the roles of RNA-binding residues in A3H activity, particle incorporation, inhibition of reverse transcriptase inhibition, and DNA cytidine deamination. IMPORTANCE APOBEC3 proteins are host factors that protect the integrity of the host genome by inhibiting retroelements as well as retroviruses, such as HIV-1. To do this, the APOBEC3H protein has evolved unique interactions with structured RNAs. Here, we studied the importance of these interactions in driving antiviral activity of APOBEC3H. Our results provide a clear picture of how RNA binding drives the ability of APOBEC3H to infiltrate new viruses and prevent synthesis of viral DNA. We also explore how RNA binding by APOBEC3H influences recognition and deamination of viral DNA and describe two possible routes by which APOBEC3H might hypermutate the HIV-1 genome. These results highlight how one protein can sense many nucleic acid species for a variety of antiviral activities.

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