Table 1. Features of selected peptides.
| Peptide Name | Peptide Choice Rationale | Gene name | Sequence | Activation | Inhibition | Phospho | Average SLiMPred |
Max SLiMPred | SLiMPrints |
|---|---|---|---|---|---|---|---|---|---|
| pal-ITGA2B_JM | Interaction[21] | ITGA2B | pal-KVGFFKR-(NH2) | 17* | 50 | R | 0.23 | 0.3 | - |
| pal-ITGA2B_tail | Interaction[23] | ITGA2B | pal-LEEDDEEGE | 2 | 52 | 0.13 | 0.43 | - | |
| pal-ITGB3_tail | Interaction[24] | ITGB3 | pal-TNITYRGT | 3 | 71 | 0.01 | 0.04 | - | |
| pal-ITGB3_JM | Interaction[25] | ITGB3 | pal-KLLITIHDRKE-(NH2) | 4 | 73 | 0.03 | 0.06 | - | |
| pal-ITGB3_middle1 | Interaction[26] | ITGB3 | pal-FAKFEEERAR-(NH2) | 0 | 45 | 0.04 | 0.2 | - | |
| pal-ITGB3_middle2 | Interaction[24] | ITGB3 | pal-NNPLYKEA-(NH2) | 1 | 74 | 0.16 | 0.41 | 0.6 | |
| pal-SDC4_JM | SLiMPred; Interaction[27] | SDC4 | pal-RMKKKDEGSYD-(NH2) | 0 | 4* | 0.41 | 0.64 | - | |
| pal-SDC4_middle | Interaction[27] | SDC4 | pal-LGKKPIYKK-(NH2) | 0 | 3* | 0.13 | 0.25 | - | |
| pal-SDC4_tail | SLiMPred; Interaction[27] | SDC4 | pal-APTNEFYA | 7 | 34* | 0.51 | 0.71 | - | |
| Tat | Interaction[24] | tat-(NH2) | 3 | 73 | 0.07 | 0.16 | |||
| TGFB1I1_LD-tat | SLiMPrints; SLiMPred; Interaction[28] | TGFB1I1 | TLELDRLMASLSDFRVQNHLP-tat-(NH2) | 3 | 66 | R | 0.15 | 0.57 | 0.004 |
| tat-ACTN1_VBS | Interaction[29] | ACTN1 | tat-WEQLLTTIARTINEVENQI-(NH2) | 66* | 61* | R | 0.04 | 0.22 | - |
| tat-VCL | SLiMPred, Interaction[30] | VCL | tat-EPDFPPPPPDLE-(NH2) | 4 | 70 | 0.58 | 0.88 | 0.14 | |
| tat-VASP | SLiMPrints; Interaction[31] | VASP | tat-AGAKLRKVSKQE-(NH2) | 3 | 74 | 0.22 | 0.49 | 0.01 | |
| tat-CAST_1 | Interaction[32] | CAST | tat-DPMSSTYIEELGKREVTIPPKYRELLA-(NH2) | 3 | 72 | A | 0.06 | 0.2 | - |
| tat-CAST_2 | SLiMPred; Interaction[33] | CAST | tat-SKPIGPDDAIDALSSDFTS-(NH2) | 3 | 74 | 0.18 | 0.59 | - | |
| tat-MSN | Interaction[34] | MSN | tat-GRDKYKTLRQIRQGNTKQRIDEFESM | 3 | 73 | 0.1 | 0.41 | 0.07 | |
| tat-NHERF1 | SLiMPrints; Interaction[35] | NHERF1 | tat-KRAPQMDWSKKNELFSNL | 3 | 70 | 0.18 | 0.44 | 0.04 | |
| tat-FAK_1 | Interaction[36] | PTK2/ FAK1 |
tat-EGERALPSIPKLAN-(NH2) | 4 | 72 | 0.07 | 0.23 | - | |
| tat-FAK_2 | SLiMPrints; Interaction[36] | PTK2/ FAK1 |
tat-SVSETDDpYAEIIDE-(NH2) | 3 | 71 | 0.06 | 0.17 | 0.001 | |
| AMAP1-tat | SLiMPrints; Interaction[37] | ASAP1/ DDEF2 |
SSTLSKKRPPPPPPGHKRTLSD-tat-(NH2) | 4 | 72 | 0.25 | 0.49 | 0.002 | |
| PTPN1-tat | SLiMPrints | PTPN1 | GIESMSQDTEVRSRVVGGS-tat | 3 | 77 | 0.14 | 0.37 | <0.00001 | |
| INPP5D-tat | SLiMPred; SLiMPrints | INPP5D | KLSQLTSLLSSIE-tat | 4 | 74 | 0.46 | 0.9 | 0.01 | |
| PTPN12-tat | SLiMPred; SLiMPrints | PTPN12 | NSDTPPRPDRLPL-tat | 3 | 75 | 0.48 | 0.89 | 0.003 |
Identification of peptides modulating platelet aggregation. Pal: peptides are N-terminally palmitylated (peptides tested at 20μM). tat: addition to the peptide of the cell-penetrating peptide sequence GRKKRRQRRRPPQ at the indicated terminus (peptides tested at 50μM). Activation: platelet aggregation induced in resting platelets after 6 minutes incubation with peptides, quantified as optical density using an aggregometer, n> = 3. Inhibition: platelet aggregation induced by 4μM TRAP in platelets pre-incubated with peptide. Phospho: Phosphorylation changes associated with peptide treatment, R: in resting platelets, A: after TRAP activation. Underlined bold residues represent known phosphorylation sites: the tat-FAK_2 peptide was synthesized in its phosphorylated form (indicated by Y preceded with a lower case p). Cell delivery mechanisms are indicated as pal and tat. JM = juxtamembrane. Peptide Choice Rationale: “Interaction” indicates that there is an experimental evidence that residues in this peptide are involved in adhesome protein-protein interactions; “SLiMPred” indicates a maximum score for a residue in the peptide > 0.5; and “SLiMPrints” indicates a significance (Sig) score of less than 0.05 for a motif within or overlapping the peptide.
*: significantly (p≤0.05; see S1 Fig) higher aggregation than resting platelets (activation column) or lower than TRAP-activated platelets (inhibition column).