title: Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate-Pam3Cys conjugates as TLR2 agonists.
abstract: Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6 e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate-Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant.
authors.affiliation: Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Naresh
authors.initials: N
authors.lastname: Nalla
authors.affiliation: Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Preethi
authors.initials: P
authors.lastname: Pallavi
authors.affiliation: Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Bonam Srinivasa
authors.initials: BS
authors.lastname: Reddy
authors.affiliation: Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Miryala
authors.affiliation: Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: V
authors.initials: V
authors.lastname: Naveen Kumar
authors.affiliation: Toxicology Laboratory, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mahboob
authors.affiliation: Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: sampath@iict.res.in.
authors.forename: M Sampath Kumar
authors.initials: MS
authors.lastname: Halmuthur
mesh_terms: D015195:Drug Design; D008074:Lipoproteins / Q000378:metabolism*; D010455:Peptides; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D008074:Lipoproteins; D010455:Peptides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014230:Triazoles; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine
keywords: Adjuvants; Carbohydrate; Click chemistry; Cytokines; Pam(3)Cys