Table 1.
Peptide structure-activity-relationship and solubility.
| Peptide | Sequence | Cell (Aβ lowering) IC50 (nM) |
Solubility pH 6.5 (μg/mL) |
|---|---|---|---|
| Pep#1 | Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-NH2 | inactive (> 40 μM) | – |
| Pep#2 | Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys-NH2 | inactive (> 40 μM) | – |
| Pep#3 | Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(ε-Chol'ester’)-NH2 | 0.40 | > 3000 |
| Pep#4 | Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(ε-Palmitoyl)-NH2 | 6.0 | < 1.0 |
| Pep#5 | Ac-Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-NH2 | Inactive (> 40 μM) | – |
| Pep#6 | Ac-Tyr-Pro-Tyr-Phe-Leu-Pro-Ile-Ser-Ala-Lys-NH2 | inactive (> 40 μM) | – |
| Pep#6a | Ac-Ala-Leu-Tyr-Pro-Tyr-Phe-Leu-Pro-Ile-Ser-Ala-Lys-NH2 | a | |
| Pep#7 | Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Chol'ester’)-NH2 | 0.027 | < 1.0 |
| Pep#8 | Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-NH(CH2)5CO-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Chol'ester’)-NH2 | 0.075 | – |
| Pep#9 | Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Chol'ester’)-NH2 | 0.006 | > 718 |
| Pep#10 | Tyr-Pro-Tyr-Phe-Ile-Pro-Ala-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Chol'ester’)-NH2 | 0.004 | > 2450 |
| Pep#11 | Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmitoyl)-NH2 | 0.20 | > 3000 |
| Pep#12 | Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-NH2 | 19 | – |
| Pep#13 | H-Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-PEG(4)-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-NH2 | 45 | – |
| Pep#14 | Gly-Gly-Gly-Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Chol'ester’)-NH2 | 0.57 | – |
| Pep#15 | Gly-Gly-Gly-Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmitoyl)-NH2 | 0.34 | – |
| Pep#16 | Gly-Gly-Gly-Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-Asn-Sta-Val-Ala-Glu-DPro-NH2 | 6.4 | – |
a
Compound (peptide 2 in Kornacker et al., 2005) used in the ternary complex BACE1 ectodomain structure (accession code 5MCO). A KD of 0.63 μM for Pep#6a has been reported determined using a biochemical approach isothermal calorimetry (ICT).