Compound monograph
P021 (P21)
P021 is a small acetylated tetrapeptide carrying an adamantane-derived C-terminal extension, designed as a CNTF-derived peptide mimetic.
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Identity & nomenclature
P021 is a small acetylated tetrapeptide carrying an adamantane-derived C-terminal extension, designed as a CNTF-derived peptide mimetic.
P021 is the preferred research designation; P21 is the common commercial spelling. The primary literature identifies it as a peptide mimetic derived from ciliary neurotrophic factor, CNTF. It is not described there as a chemically identified fragment isolated from Cerebrolysin, and that provenance claim should not be repeated.
Declared aliases and development codes: P21, P-21, Peptide 021.
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Molecular properties
| Molecular formula | C27H42N6O8 |
|---|---|
| Molecular mass | 578.66 Da |
| CAS Registry Number | 1246751-68-7 |
| PubChem CID | 56599151 |
| UNII | VV8CZC8PAS |
| Three-letter sequence | Ac–Asp–Gly–Gly–Leu–Adamantane-carboxamide–NH2 |
CRITICAL: the shorthand Ac-DGGLAG-NH2 appears in the primary literature, where AG denotes a single adamantane-derived unit — NOT alanine followed by glycine. Parsed as an ordinary six-residue peptide it yields the wrong molecule, formula and mass. The leucine carbonyl is amide-linked to an amino-substituted adamantane cage bearing a carboxamide. The aspartate side-chain carboxyl is free.
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Structural characteristics
Reported effects are at the pathway level: LIF-related signalling, and changes in BDNF expression with associated GSK3beta signalling in experimental models. No direct molecular binding target, binding affinity, receptor-subtype selectivity or receptor-level agonist classification is established. P021 should not be described as a direct TrkB agonist or a direct GSK3beta inhibitor on the strength of downstream measurements. The proposed BDNF increase is also not uniformly reproduced: an independent study reports that chronic exposure failed to raise BDNF under its conditions. That result is part of the record for this compound, not an omission.
- Adamantane-based C-terminal extension
Terminal features: N-terminal acetylation, C-terminal carboxamide.
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Molecular targets & mechanisms
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Analytical considerations
For a molecule this size the useful identity package is LC–high-resolution MS with 1D and 2D NMR, supported by fragmentation and amino-acid analysis. NMR matters specifically because 'contains an adamantane group' does not establish the registered connectivity, and a mass-compatible connectivity isomer — including an Asp/isoAsp rearrangement — would not be excluded by an intact-mass match. Asp and Leu configuration need a chiral method. A BDNF-expression assay is not a chemical identity test and is a poor acceptance criterion given the conflicting reports above.
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Verified bibliography
- Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice.current
Li B, Wanka L, Blanchard J, Liu F, Chohan MO, Iqbal K, Grundke-Iqbal I
FEBS letters · 2010-06-30 · Journal Article
- Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease.current
Kazim SF, Blanchard J, Dai CL, Tung YC, LaFerla FM, Iqbal IG, Iqbal K
Neurobiology of disease · 2014-07-15 · Journal Article
- Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder.current
Mottolese N, Loi M, Trazzi S, Tassinari M, Uguagliati B, Candini G, Iqbal K, Medici G, Ciani E
Journal of neurodevelopmental disorders · 2024-11-26 · Journal Article
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Methodology & citation verification
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