Nemifitide: Molecular Structure
Chemical properties, amino acid sequence, and structural analysis
📌TL;DR
- •Molecular formula: C33H43FN10O6
- •Molecular weight: 694.76 Da
- •Half-life: 15-30 minutes
Amino Acid Sequence
38 amino acids
Formula
C33H43FN10O6
Molecular Weight
694.76 Da
Half-Life
15-30 minutes
Molecular Structure#
Nemifitide (INN-00835) is a synthetic pentapeptide analog of melanocyte-inhibiting factor (MIF-1). Its sequence incorporates two non-standard amino acids: 4-fluorophenylalanine at position 1 and trans-4-hydroxyproline at position 2. The C-terminal tryptophan is amidated.
Amino Acid Sequence#
| Property | Value |
|---|---|
| Sequence | 4-F-Phe-trans-4-OH-Pro-Arg-Gly-Trp-NH2 |
| Length | 5 amino acids |
| Molecular weight | ~694.76 Da |
| Molecular formula | C33H43FN10O6 |
| CAS number | 204992-09-6 (diTFA salt) |
| Parent compound | MIF-1 (Pro-Leu-Gly-NH2) |
| Salt form | DiTFA (ditrifluoroacetate) |
Key Structural Modifications#
4-Fluorophenylalanine (Position 1)#
The fluorine substitution at the para position of phenylalanine enhances lipophilicity and metabolic stability while improving receptor binding characteristics. This modification is a common strategy in peptide medicinal chemistry.
trans-4-Hydroxyproline (Position 2)#
Hydroxyproline constrains the peptide backbone conformation, potentially improving receptor selectivity and reducing conformational flexibility compared to proline in the parent MIF-1.
C-Terminal Tryptophan Amide#
The tryptophanamide C-terminus provides an indole moiety important for serotonergic receptor interaction and protects against carboxypeptidase degradation.
Pharmacokinetic Properties#
| Parameter | Details |
|---|---|
| Half-life | 15-30 minutes |
| Tmax | ~10 minutes (SC injection) |
| Bioavailability | Not orally bioavailable; SC injection required |
| Dose proportionality | AUC and Cmax approximately dose-proportional (18-320 mg range) |
| Route | Subcutaneous injection |
Phase 1 pharmacokinetic studies in healthy volunteers demonstrated rapid absorption (Cmax at 10 minutes) and elimination (half-life 15-30 minutes) after subcutaneous injection. Despite the short half-life, pharmacodynamic effects persist for days, suggesting receptor-level adaptations outlast plasma drug exposure.
Stability Characteristics#
Nemifitide is typically supplied as the ditrifluoroacetate (diTFA) salt form for stability. Lyophilized material should be stored at -20 degrees C. The compound is inactive orally, necessitating parenteral administration.
Molecular Context#
Nemifitide belongs to the Neuropeptide category of research peptides. The molecular properties of Nemifitide determine its pharmacological behavior, including receptor binding, distribution, metabolism, and elimination. Understanding these properties is fundamental to interpreting clinical data and designing research protocols.
Structural Overview#
Nemifitide is characterized as: Nemifitide is a synthetic pentapeptide with the sequence 4-fluorophenylalanyl-trans-4-hydroxyproline-arginyl-glycyl-tryptophanamide. The 4-fluorophenylalanine and trans-4-hydroxyproline are non-natural amino acid modifications that improve receptor binding affinity and metabolic stability compared to native MIF-1..
Amino Acid Sequence Details#
The amino acid sequence of Nemifitide is: 4-F-Phe-trans-4-OH-Pro-Arg-Gly-Trp-NH2. This sequence determines the peptide's three-dimensional structure, receptor binding properties, and biological activity.
Pharmacokinetic Profile#
Half-Life: 15-30 minutes
The half-life of a peptide influences dosing frequency, duration of effect, and the clinical utility of the compound. Researchers should consider the half-life when designing experimental protocols.
Related Reading#
Frequently Asked Questions About Nemifitide
What type of peptide is Nemifitide?
Nemifitide (INN-00835) is a synthetic pentapeptide analog of melanocyte-inhibiting factor (MIF-1) developed as a rapid-onset antidepressant. Clinical trials have demonstrated onset of action within 5-7 days, compared to 2-6 weeks for standard antidepressants. It is administered by subcutaneous injection and has shown a favorable safety profile in over 430 subjects across 12 clinical trials. Development has reached phase 3 but the compound has not been approved.
What is the half-life of Nemifitide?
The reported half-life of Nemifitide is 15-30 minutes. Half-life can vary depending on the route of administration, formulation, and individual factors. This information is based on available preclinical or pharmacokinetic data.
What is the amino acid sequence of Nemifitide?
The amino acid sequence of Nemifitide is 4-F-Phe-trans-4-OH-Pro-Arg-Gly-Trp-NH2. Nemifitide is a synthetic pentapeptide with the sequence 4-fluorophenylalanyl-trans-4-hydroxyproline-arginyl-glycyl-tryptophanamide. The 4-fluorophenylalanine and trans-4-hydroxyproline are non-natural amino acid modifications that improve receptor binding affinity and metabolic stability compared to native MIF-1.. This sequence determines its biological activity and binding properties.
How stable is Nemifitide in storage?
Nemifitide is typically supplied as a lyophilized powder for maximum stability. Nemifitide is a synthetic pentapeptide with the sequence 4-fluorophenylalanyl-trans-4-hydroxyproline-arginyl-glycyl-tryptophanamide. The 4-fluorophenylalanine and trans-4-hydroxyproline are non-natural amino acid modifications that improve receptor binding affinity and metabolic stability compared to native MIF-1.. When reconstituted, it should be stored refrigerated at 2-8 degrees C and protected from light. Lyophilized powder should be stored at -20 degrees C.
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