1.O6-(benzotriazol-1-yl)inosine derivatives for C6 modification of purine nucleosides.
Bae S1, Chaturvedi S, Lakshman MK. Curr Protoc Nucleic Acid Chem. 2009 Mar;Chapter 1:Unit 1.22. doi: 10.1002/0471142700.nc0122s36.
A new class of reactive nucleosides, O(6)-(benzotriazol-1-yl) derivatives of inosine and 2'-deoxyinosine, have been developed via reaction of silyl-protected or unprotected inosine and 2'-deoxyinosine with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). Alternatively, the silyl-protected O(6)-(benzotriazol-1-yl) derivatives can be synthesized via reaction of protected inosine and 2'-deoxyinosine with triphenylphosphine/iodine/1-hydroxybenzotriazole. These new O(6)-(benzotriazol-1-yl) inosine derivatives are excellent reagents for the synthesis of other nucleoside analogues via S(N)Ar reaction with a range of nucleophiles.
2.One-pot etherification of purine nucleosides and pyrimidines.
Kokatla HP1, Lakshman MK. Org Lett. 2010 Oct 15;12(20):4478-81. doi: 10.1021/ol101655h.
A one-pot synthesis of ethers derived from inosine, guanosine, 2'-deoxyguanosine, and pyrimidinones is described. Exposure of the heterocycle to 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and Cs(2)CO(3) produces a reactive intermediate, which is converted to the desired ether by subsequent addition of an appropriate alcohol or phenol and Cs(2)CO(3). Although rapid formation of HMPA from BOP can occur in the presence of an alcohol and base, as demonstrated by the reaction with methanol, under appropriate conditions these heteroaryl ethers can be efficiently synthesized.
3.Coupling strategies for the synthesis of Peptide-oligonucleotide conjugates for patterned synthetic biomineralization.
Carter JD1, Labean TH. J Nucleic Acids. 2011;2011:926595. doi: 10.4061/2011/926595. Epub 2011 Oct 9.
This work describes preparation strategies for peptide-oligonucleotide conjugates that combine the self-assembling behavior of DNA oligonucleotides with the molecular recognition capabilities of peptides. The syntheses include a solution-phase fragment coupling reaction and a solid-phase fragment coupling strategy where the oligonucleotide has been immobilized on DEAE Sepharose. The yield of four coupling reagents is evaluated, two reagents in water, EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) and DMTMM (4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride), and two in dimethylformamide (DMF), PyBOP ((Benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate) and HBTU (O-benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate), while the oligonucleotide fragment is either in solution or immobilized on DEAE. These coupling strategies rely on an unprotected 5' amino linker on the oligonucleotide reacting with the peptide C-terminus.
4.Signal transduction of hyaluronic acid-peptide conjugate for formyl peptide receptor like 1 receptor.
Oh EJ1, Kim JW, Kong JH, Ryu SH, Hahn SK. Bioconjug Chem. 2008 Dec;19(12):2401-8. doi: 10.1021/bc800255y.
Agonistic and antagonistic peptides for formyl peptide receptor like 1 (FPRL1) receptor have been investigated as novel drug candidates for inflammatory diseases such as sepsis, asthma, and rheumatoid arthritis. In this work, a novel protocol for the synthesis of hyaluronic acid (HA)-peptide (CWRYMVm) conjugate for FPRL1 receptor was successfully developed for further clinical applications of peptide drugs. Aminoethyl methacrylated HA (HAAEMA) was synthesized by the coupling reaction of tetrabutyl ammonium salt of HA (HA-TBA) and AEMA using benzotriazol-1-yloxy-tris(dimethylamino) phosphonium hexafluorophosphate (BOP) in dimethyl sulfoxide (DMSO). Then, HA-AEMA was conjugated with CWRYMVm in water via Michael addition reaction between methacrylate group of HA-AEMA and thiol group in cysteine. The formation of HA-peptide conjugate was confirmed by 1H NMR and gel permeation chromatography (GPC). The average number of conjugated peptide molecules could be controlled from 5 to 23 per single HA chain.
