Table 1.
Analogues of the bradykinin potentiating peptide BPP9α (TEPROTIDE) with distinct differences between potentiation of the BK-induced contraction of the isolated guinea pig ileum (GPI) and inhibition of the isolated angiotensin I-converting enzyme (ACE)
| Compound | Aminoacid sequence | Potentiation (%) | ACE-inhibition: IC50 (M) | Quotient |
|---|---|---|---|---|
| BPP9α | Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro | 100 | 3 × 10−9 | 7.0 |
| Pro-Trp-Pro-Phe-Pro-Gln-Tyr-Pro-Pro | 100 | 8 × 10−9 | 19 | |
| Pro-Trp-Pro-Leu-Pro-Lys-Tyr-Pro-Pro | 100 | 6 × 10−8 | 0.1 × 103 | |
| Pro-Trp-Pro-Leu-Pro-Gln-Ile-Pro-Pro | 90 | 1 × 10−5 | 2.5 × 104 | |
| [1-Pro]-BPP9α | Pro-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro | 115 | 5 × 10−10 | 1 |
| Pro-Trp-Pro-Arg-Pro-Gln-Ile-Ala-Pro | 70 | 3 × 10−7 | 1 × 103 | |
| Pro-Trp-Ala-Arg-Pro-Gln-Ile-Pro-Pro | 75 | 3 × 10−8 | 93 | |
| Pro-Trp-Pro-Leu-Pro-Leu-Ile-Pro-Pro | 50 | 1 × 10−7 | 0.5 × 103 | |
| Pro-Trp-Pro-Phe-Pro-Gln-Ile-Pro-Pro | 90 | 5 × 10−8 | 0.1 × 103 | |
| J527 | Pro-Trp-Pro-Lys-Pro-Gln-Ile-Pro-Pro | 70 | 3 × 10−8 | 0.1 × 103 |
| Pro-Trp-Pro-Lys-Pro-Lys-Ile-Pro-Pro | 75 | 2 × 10−8 | 63 | |
| Pro-Trp-Pro-Lys-Pro-Lys-Tyr-Pro-Pro | 90 | 5 × 10−5 | 1.3 × 105 | |
| Pro-Trp-Pro-Leu-Pro-Lys-Ile-Pro-Pro | 85 | 3 × 10−8 | 82 | |
| Pro-Trp-Pro-Phe-Pro-Gln-Ile-Ala-Pro | 70 | 3 × 10−6 | 1.0 × 104 | |
| Pro-Trp-Pro-Phe-Pro-Gln-Tyr-Ala-Pro | 58 | 3 × 10−8 | 0.1 × 103 | |
| Pro-Trp-Pro-Arg-Pro-Gln-Tyr-Pro-Pro | 76 | 2 × 10−8 | 61 | |
| Pyr-Trp-Pro-Lys-Pro-Gln-Ile-Pro-Pro | 65 | 2 × 10−8 | 72 | |
| Pro-Trp-Pro-Arg-Pro-Lys-Ile-Pro-Pro | 50 | 7 × 10−8 | 0.3 × 103 | |
| Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro | 65 | 2 × 10−8 | 71 | |
| Leu-Pro-Gln-Ile-Pro-Pro | 40 | 7 × 10−6 | 4.0 × 104 | |
| Arg-Pro-Gln-Ile-Pro-Pro | 55 | 7 × 10−6 | 3.0 × 104 | |
| Analogues and partialsequences with the photolabels ASAa and ABAb | ||||
| ABA-Pro-Trp-Pro-Phe-Pro-Gln-Tyr-Pro-Pro | 93 | 1 × 10−7 | 0.3 × 103 | |
| ASA-Pro-Trp-Pro-Leu-Pro-Gln-Ile-Pro-Pro | 110 | 3 × 10−7 | 0.7 × 103 | |
| ASA-Pro-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro | 90 | 6 × 10−9 | 16 | |
| Pro-Trp-Pro-Lys(ASA)-Pro-Lys-Ile-Pro-Pro | 99 | 1 × 10−8 | 23 | |
| Pro-Trp-Pro-Lys-Pro-Lys(ASA)-Ile-Pro-Pro | 103 | 8 × 10−8 | 0.2 × 103 | |
| Pro-Trp-Pro-Lys(ABA)-Pro-Lys-Tyr-Pro-Pro | 88 | 3 × 10−8 | 79 | |
| Pro-Trp-Pro-Leu-Pro-Lys(ASA)-Ile-Pro-Pro | 86 | 5 × 10−7 | 1.4 × 103 | |
| ABA-Pro-Trp-Pro-Phe-Pro-Gln-Tyr-Ala-Pro | 20 | 1 × 10−5 | 1.1 × 105 | |
| J526 | Pyr-Trp-Pro-Lys(ASA)-Pro-Gln-Ile-Pro-Pro | 160 | 7 × 10−5 | 1.0 × 105 |
| ASA-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro | 110 | 6 × 10−8 | 0.1 × 103 | |
| ASA-Leu-Pro-Gln-Ile-Pro-Pro | 70 | 8 × 10−6 | 2.6 × 104 | |
| ASA-Arg-Pro-Gln-Ile-Pro-Pro | 40 | 4 × 10−5 | 2.3 × 105 | |
| Analogues with the photolabel Bpac | ||||
| Bpa-Pro-Trp-Pro-Lys-Pro-Lys-Tyr-Pro-Pro | 70 | 7 × 10−5 | 2.3 × 105 | |
| Bpa-Pro-Trp-Pro-Lys-Pro-Lys-Tyr(I)-Pro-Pro | 75 | 5 × 10−8 | 0.2 × 103 | |
| Bpa-Pro-Trp-Pro-Phe-Pro-Gln-Tyr-Ala-Pro | 20 | 1 × 10−6 | 1.1 × 104 | |
| Bpa-Pro-Trp-Pro-Arg-Pro-Gln-Tyr-Pro-Pro | 72 | 2 × 10−8 | 65 | |
| Pro-Bpa-Pro-Arg-Pro-Gln-Tyr-Pro-Pro | 63 | 2 × 10−8 | 74 | |
| Pro-Trp-Pro-Bpa-Pro-Gln-Tyr-Pro-Pro | 90 | 3 × 10−8 | 77 | |
To quantify the difference between potentiation and inhibition we calculated a quotient from both activities. For the analogue with the highest ACE-inhibitory activity [1-Pro]-BPP9α the quotient was accounted to 1.
a
4-Azidosalicylic acid.
b
4-Azidobenzoic acid.
c
p-Benzoylphenylalanine.