Inhibition of angiotensin-converting enzyme by analogs of peptides fromBothrops jararaca venom

Zusammenfassung Nachweis mit Analogen der im Gifte vonBothrops jararaca gefundenen Peptide, dass die Inhihibition des Angiotensins «converting enzyme» von zwei eindeutigen Teilsequenzen dieser Peptide abhängig ist. Die hohe spezifische kompetitive Inhibition, hervorgerufen durch die Peptide vonBothrops jararaca, wird der Bindung ihrer Tripeptidreste vom Carboxyterminus mit dem aktiven Zentrum des Enzyms zugeschrieben, die in gleicher Weise wie die Peptidsubstrate mit dem Enzym gebunden werden. Die Wirksamkeit der Giftpeptide hängt von der Bindung eines zweiten Teiles der Peptide mit dem Enzym ab.     

Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha(+)-thalassemia. Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa.