Usage Of Topological Indexes In The Study Of Biologically Active Peptides: Tuftsin And Its Analogues
Vladislav V. Kholodovich
Institute of Bioorganic Chemistry & Petrochemistry, Kiev,
UKRAINE
75 compounds were collected from the literature with the
aim to describe structure -activity relationships of
phagocytosis-stimulating peptide tuftsin (Thr-Lys-Pro-Arg) and
its analogues. Whole set of compounds was divided on three
subgroups. First subgroup includes active compounds that
stimulate phagocytosis of leukocytes more than 10%. Second
subgroup is formed with the non active compounds (stimulating
less than 10%). These two subgroups were used for the training
purposes. The result of work of training algorithm was tested
on the third group, which contains molecules that not used in
the training set. 270 different topological indexes, including
original, were calculated for describing phagocytosis-
stimulating activity. By using the modified method of k-
neighbors, the genetic algorithm was suggested, the initial
set of indexes was reduced to 7 more important indexes, which
explained 90% of the activity of the training set. Obtained
indexes were tested on the third subgroup and showed good
results (only one compound was predicted wrongly). Ten new
analogues of tuftsin were synthesized in our laboratory with
the aim of obtaining compounds more effective in the
stimulation of immune system than tuftsin. The reduced set of
indexes was used for the prediction of biological activities
of new synthesized compounds. In the biological test about 80%
of new compounds confirmed previously calculations (predicted
correctly 8 from 10). The presented study shows that the
integrity of the N terminus is not mandatory for full
biological tuftsin-like activity. Our data also suggest that
the dipeptide analogues X-Arg-OMe, where X is non-natural
amino acid and OMe is methyl ester, are promising agents for
immunotherapy, while dipeptide Pro-Arg-OMe, which is the
reduced amino acid chain of tuftsin, can be used as inhibitor
of phagocytosis stimulation. On the other hand found set of 7
parameters may prove to be useful for correlation studies in
series of bioactive peptide analogues and helpful tool in the
determining tuftsin receptors.
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