FAM-Ahx-NYAD-1 (NYAD-2)
Antiviral Peptides
FAM-Ahx-NYAD-1 (NYAD-2) is a FAM-labeled (Ex/Em = 495/520 nm) cell-penetrating α-helical peptide developed as a potential HIV-1 inhibitor. The hydrocarbon staple stabilizes the α-helical conformation and enhances structural rigidity. To preserve these properties, the FAM label is attached via an Ahx spacer (6-aminohexanoic acid, CAS: 60-32-2). This flexible linker reduces steric interference between the fluorophore and the peptide backbone, ensuring optimal binding and accurate cellular imaging.
Disease Target
Targets HIV-1 infection (AIDS) by disrupting viral capsid assembly. This FAM-labeled analog enables cellular uptake and intracellular tracking while retaining inhibitory activity against HIV-1 capsid formation.
Stapling Strategy
FAM-Ahx-NYAD-1 (NYAD-2) is synthesized by incorporating Fmoc-(S)-2-(4-pentenyl)alanine (Fmoc-(S5)-OH, CAS: 288617-73-2) at the i,i+4 positions within the CAI-derived sequence during solid-phase peptide synthesis (SPPS). The stapled structure is generated via ruthenium-catalyzed ring-closing olefin metathesis, forming a hydrocarbon constraint that stabilizes the α-helical conformation. An N-terminal FAM label (Ex/Em = 495/520 nm) is introduced through an Ahx spacer, using 6-aminohexanoic acid (Ahx, CAS: 60-32-2) as a flexible linker to separate the fluorophore from the peptide backbone, thereby reducing potential steric interference and preserving the peptide’s binding and conformational properties. This design enables fluorescence-based cellular imaging and uptake studies.
Technical specification
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Sequency : | FAM-Ahx-ITF(S5)DLL(S5)YYGP-NH2 |
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MW : | 1950.23 g/mol |
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Purity : | > 95% |
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Counter-Ion : | TFA Salts |
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Delivery format : | Lyophilized |
Price
| Product | Size | Price € |
Price $ |
| SB333-1mg | 1 mg | 692 | 802 |
| SB333-5mg | 5 mg | 841 | 981 |
| SB333-10mg | 10 mg | 1088 | 1278 |
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An unlabeled version of this peptide is available for applications not requiring fluorescence. Tap the button below to view the non-conjugated product.
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References
2008 May 2;378(3):565-80. doi: 10.1016/j.jmb.2008.02.066. Epub 2008 Mar 6.
A cell-penetrating helical peptide as a potential HIV-1 inhibitor
Abstract
The capsid domain of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein is a critical determinant of virus assembly, and is therefore a potential target for developing drugs for AIDS therapy. Recently, a 12-mer alpha-helical peptide (CAI) was reported to disrupt immature- and mature-like capsid particle assembly in vitro; however, it failed to inhibit HIV-1 in cell culture due to its inability to penetrate cells. The same group reported the X-ray crystal structure of CAI in complex with the C-terminal domain of capsid (C-CA) at a resolution of 1.7 A. Using this structural information, we have utilized a structure-based rational design approach to stabilize the alpha-helical structure of CAI and convert it to a cell-penetrating peptide (CPP). The modified peptide (NYAD-1) showed enhanced alpha-helicity. Experiments with laser scanning confocal microscopy indicated that NYAD-1 penetrated cells and colocalized with the Gag polyprotein during its trafficking to the plasma membrane where virus assembly takes place. NYAD-1 disrupted the assembly of both immature- and mature-like virus particles in cell-free and cell-based in vitro systems. NMR chemical shift perturbation analysis mapped the binding site of NYAD-1 to residues 169-191 of the C-terminal domain of HIV-1 capsid encompassing the hydrophobic cavity and the critical dimerization domain with an improved binding affinity over CAI. Furthermore, experimental data indicate that NYAD-1 most likely targets capsid at a post-entry stage. Most significantly, NYAD-1 inhibited a large panel of HIV-1 isolates in cell culture at low micromolar potency. Our study demonstrates how a structure-based rational design strategy can be used to convert a cell-impermeable peptide to a cell-permeable peptide that displays activity in cell-based assays without compromising its mechanism of action. This proof-of-concept cell-penetrating peptide may aid validation of capsid as an anti-HIV-1 drug target and may help in designing peptidomimetics and small molecule drugs targeted to this protein.
