RESUMO
Natural tetrapeptide Goralatide (AcSDKP) is a selective inhibitor of primitive haematopoietic cell proliferation. It is not stable in vivo and decomposes within 4.5min when applied to live cells. In this work we developed an analog of Goralatide that exhibits cytotoxicity towards human myeloid HL-60, HEL, Nalm-6 leukemia cells, endothelial HUVEC, glioblastoma U251 and transformed kidney 293T cells. The Goralatide analog showed significant stability in organic solution with no tendency to degrade oxidatively.
Assuntos
Antineoplásicos/síntese química , Oligopeptídeos/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Células HL-60 , Células Endoteliais da Veia Umbilical Humana , Humanos , Oligopeptídeos/síntese química , Oligopeptídeos/toxicidadeRESUMO
The temperature-dependent (1)H and (13)C NMR spectra of 2-(2-butynyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole (4) (as a representative example of 1-9) in CFCl(3) + CD(2)Cl(2) solution are described and discussed. Below 183 K, the hexahydropyrazine ring inversions become slow on the NMR time-scale and 4 exists in principle as two conformational diastereomers. In fact, only one was observed with the N-2 substituent in an equatorial position as shown by a low-temperature NOESY experiment. The energy barrier for conformational interchange was calculated from NMR data to be 8.3 kcal mol(-1) (1 kcal = 4.184 kJ), in agreement with quantum chemical calculations. Unambiguous assignments for all proton and carbon resonances of 1-9 were made using 1D (APT, DEPT, NOE difference) and 2D (COSY, NOESY, gHMQC, gHMBC) NMR techniques.