Atherton F R, Hall M J, Hassall C H, Holmes S W, Lambert R W, Lloyd W J, Ringrose P S
Antimicrob Agents Chemother. 1980 Dec;18(6):897-905. doi: 10.1128/AAC.18.6.897.
Dipeptide variants of alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) with substantial differences in potency and antibacterial spectrum in vitro and in vivo have been synthesized. Certain dipeptides with alternatives to the L-alanyl residue had broader antibacterial spectra; activity against Pseudomonas aeruginosa was included. Some compounds had better in vivo activity than alafosfalin when introduced into infected rodents orally, but for the majority of the more active phosphonodipeptides, parenteral administration was more effective. Certain oligopeptides derived from the more active phosphonodipeptides possessed good in vitro activity against an extended range of organisms; they included Haemophilus influenzae, Streptococcus faecalis, and Streptococcus pneumoniae. The in vivo activity of some of these phosphono-oligopeptides was significantly greater than that of the parent dipeptide and correlated well with the in vitro results. This indicates that phosphono-oligopeptides exert part of their in vivo action directly, in addition to that arising from smaller peptides produced by peptidase cleavage.
已合成了丙氨磷（L-丙氨酰-L-1-氨基乙基膦酸）的二肽变体，它们在体外和体内的效力及抗菌谱存在显著差异。某些用其他基团替代L-丙氨酰残基的二肽具有更广泛的抗菌谱，包括对铜绿假单胞菌的活性。一些化合物经口服引入感染的啮齿动物体内时，其体内活性比丙氨磷更好，但对于大多数活性更高的膦二肽而言，肠胃外给药更为有效。源自活性更高的膦二肽的某些寡肽对多种生物体具有良好的体外活性，其中包括流感嗜血杆菌、粪肠球菌和肺炎链球菌。这些膦寡肽中的一些在体内的活性明显高于母体二肽，并且与体外结果相关性良好。这表明，膦寡肽除了通过肽酶裂解产生的较小肽发挥作用外，还直接发挥其部分体内作用。
