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Org Lett ; 21(9): 3265-3270, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30986070


A traceless ß-mercaptan-assisted α-selective ligation of N-terminal lysine-containing peptides has been developed. In this ligation-desulfurization-based protocol, the ε-amine of lysine is free of protection, thus improving the overall synthetic efficiency and avoiding harsh reactions in preparing large peptides and proteins. The applicability of this methodology has been demonstrated in the synthesis of an acid-labile therapeutic protein, interferon gamma, and the anticancer activity of synthetic protein has also been evaluated.

Antineoplásicos/síntese química , Interferon gama/síntese química , Lisina/química , Aminas/química , Antineoplásicos/farmacologia , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Interferon gama/farmacologia , Conformação Proteica , Técnicas de Síntese em Fase Sólida , Compostos de Sulfidrila/química
Chem Commun (Camb) ; 55(2): 253-256, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30534737


We describe the preparation of a cancer vaccine candidate by conjugating a MUC1 peptide antigen to the ß-glucan polysaccharide, which serves both as a carrier and an immune activator. In contrast to amorphous polysaccharides, peptide-ß-glucan conjugates form uniform nanoparticles that facilitate the delivery of antigens and binding to myeloid cells, thus leading to the activation of both innate and adaptive immunity.

Adenocarcinoma/imunologia , Vacinas Anticâncer/imunologia , Portadores de Fármacos/química , Mucina-1/imunologia , Fragmentos de Peptídeos/imunologia , beta-Glucanas/química , Imunidade Adaptativa/imunologia , Sequência de Aminoácidos , Animais , Vacinas Anticâncer/síntese química , Vacinas Anticâncer/química , Humanos , Imunidade Ativa/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Interferon gama/metabolismo , Interleucina-6/metabolismo , Células MCF-7 , Camundongos Endogâmicos C57BL , Mucina-1/química , Fragmentos de Peptídeos/química , Vacinas de Subunidades/síntese química , Vacinas de Subunidades/química , Vacinas de Subunidades/imunologia , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia
Chem Sci ; 9(7): 1940-1946, 2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29675240


Peptidyl thioesters or their surrogates with C-terminal ß-branched hydrophobic amino acid residues usually exhibit poor reactivities in ligation reactions. Thus, activation using exogenous additives is required to ensure an acceptable reaction efficiency. Herein, we report a traceless ligation at Val-Xaa sites under mild thiol additive-free reaction conditions, whereby the introduction of ß-mercaptan on the C-terminal valine residue effectively activates the otherwise unreactive N-acyl-benzimidazolinone (Nbz), and enables the use of a one-pot ligation-desulfurization strategy to generate the desired peptide products. The orthogonality between ß-thiovaline-Nbz and a conventional alkyl thioester, as well as the convenient access to the former from readily available penicillamine, also allowed expedited assembly of the peptidic hormone ß-LPH and hPTH analogues, based on a kinetically controlled one-pot three-segment ligation and desulfurization strategy.