Table 1.
Structures of cytotoxic BN analogs and carriers and their ability to displace [125I-Tyr4]BN binding to BN/GRP receptors on Swiss 3T3 cells
| Structure | Receptor binding Ki,* nM |
|---|---|
| B1 = [d-Tpi6,13 ψ14, CH2-NH, Leu14]BN-(6-14) | 3.5 |
| AN-253 = DOX-14-O-glt-B1 | 8.0 |
| AN-254 = 2-pyrrolino-DOX-14-O-glt-B1 | 13.0 |
| B2 = [d-Phe6,13 ψ14,CH2-NH, Phe14]BN-(6-14) | 4.3 |
| AN-246 = DOX-14-O-glt-B2 | 4.9 |
| AN-247 = 2-pyrrolino-DOX-14-O-glt-B2 | 8.6 |
| B3 = [d-Phe6,13 ψ14,CH2-N, Tac14]BN-(6-14) | 2.7 |
| AN-161 = DOX-14-O-glt-B3 | 2.9 |
| AN-257 = 2-pyrrolino-DOX-14-O-glt-B3 | 3.4 |
| B4 = [13 ψ14,CH2-NH, Leu14]BN-(7-14) | >1000 |
| AN-160 = DOX-14-O-glt-B4 | 0.95 |
| AN-215 = 2-pyrrolino-DOX-14-O-glt-B4 | 1.6 |
| B5 = [13 ψ14,CH2-N, Tac14]BN-(7-14) | >1000 |
| AN-251 = DOX-14-O-glt-B5 | 0.7 |
| AN-252 = 2-pyrrolino-DOX-14-O-glt-B5 | 0.6 |
| BN = pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp- | 2.0† |
| Ala-Val-Gly-His-Leu-Met-NH2 |
Tac, thiazolidine-4-carboxylic acid; Tpi, 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]-indole-3-carboxylic acid
*
Varying amounts of unlabeled peptide were used to determine the ability to displace [125I-Tyr4]BN binding; mean values of two or more independent tests (each performed in triplicate) are indicated (14).
†
Mean value of 12 independent tests.