Introduction to peptidomimetics MCQs With Answer

Introduction: Introduction to peptidomimetics MCQs With Answer is designed for M.Pharm students to deepen understanding of peptidomimetics — synthetic molecules that mimic peptide structure and function. This blog covers design strategies, classification (peptoids, β-peptides, peptidomimetics with constrained backbones), methods to enhance stability and bioavailability, and therapeutic applications. Questions emphasize structure–activity relationships, synthetic modifications (N‑methylation, stapling, cyclization), protease resistance, and pharmacokinetic impacts. The set balances conceptual theory and applied formulation considerations relevant to protein and peptide drug development, preparing students for advanced coursework, exams, and research in peptide-based therapeutics and formulation science.

Q1. What is the primary goal of designing a peptidomimetic?

• To increase the molecular weight of the peptide
• To exactly replicate the full amino acid sequence of a protein
• To mimic the biological activity of a peptide while improving stability and pharmacokinetics
• To prevent any interaction with biological receptors

Correct Answer: To mimic the biological activity of a peptide while improving stability and pharmacokinetics

Q2. Which modification is commonly used to enhance proteolytic stability of peptidomimetics?

• C-terminal glycosylation
• N-methylation of amide bonds
• Introduction of additional free amide bonds
• Removal of all side chains

Correct Answer: N-methylation of amide bonds

Q3. Which class of peptidomimetics replaces the peptide backbone with N-substituted glycine units?

• β-peptides
• Peptoids
• Stapled peptides
• Macrocyclic peptides

Correct Answer: Peptoids

Q4. β-peptides differ from α-peptides by having the amino group attached to which carbon?

• Alpha carbon (Cα)
• Beta carbon (Cβ)
• Gamma carbon (Cγ)
• Delta carbon (Cδ)

Correct Answer: Beta carbon (Cβ)

Q5. What is a major pharmacokinetic advantage of cyclization in peptidomimetics?

• Increases renal clearance rate
• Decreases membrane permeability
• Improves metabolic stability and sometimes enhances oral bioavailability
• Eliminates receptor binding

Correct Answer: Improves metabolic stability and sometimes enhances oral bioavailability

Q6. “Stapled peptides” most commonly stabilize which secondary structure?

• Omega loop
• Helix (alpha-helix)
• S-sheet
• Random coil

Correct Answer: Helix (alpha-helix)

Q7. Which of the following is a typical synthetic strategy used to prepare peptoids?

• Solid-phase synthesis via the submonomer method
• Recombinant DNA expression in E. coli
• Enzymatic ligation using proteases
• Direct ribosomal translation without modification

Correct Answer: Solid-phase synthesis via the submonomer method

Q8. Which property is most commonly improved by replacing an amide bond with a non-peptidic isostere?

• Color and odor of the molecule
• Affinity for water only
• Resistance to proteolytic cleavage and altered conformational preferences
• Charge neutrality at physiological pH

Correct Answer: Resistance to proteolytic cleavage and altered conformational preferences

Q9. Which of the following is an example of a backbone-modified peptidomimetic?

• N-terminal acetylated peptide
• Peptide containing a reduced amide (ψ[CH2–NH]) linkage
• Peptide with extra glycine residues
• Unmodified linear peptide

Correct Answer: Peptide containing a reduced amide (ψ[CH2–NH]) linkage

Q10. In structure–activity relationship (SAR) studies of peptidomimetics, which change is most often examined to probe receptor binding?

• Changing salt concentration of formulation
• Systematic substitution of side-chain mimetics to map pharmacophores
• Varying the altitude at which synthesis is performed
• Switching to a completely unrelated small molecule

Correct Answer: Systematic substitution of side-chain mimetics to map pharmacophores

Q11. Which technique is frequently used to determine the conformation of peptidomimetics in solution?

• Gas chromatography–mass spectrometry (GC-MS)
• Nuclear magnetic resonance (NMR) spectroscopy
• Thermogravimetric analysis
• Flame photometry

Correct Answer: Nuclear magnetic resonance (NMR) spectroscopy

Q12. Which modification often increases cell permeability of peptidomimetics?

• Increasing the number of charged residues
• Conjugation to bulky hydrophilic polymers only
• Incorporation of lipophilic side chains and reduction of polar surface area
• Substituting all residues with proline

Correct Answer: Incorporation of lipophilic side chains and reduction of polar surface area

Q13. Which term describes peptidomimetics that mimic only the spatial arrangement of critical side chains (pharmacophore) rather than the entire peptide backbone?

• Backbone mimetics
• Pharmacophore mimetics
• Macrocyclic peptides
• Peptide dendrimers

Correct Answer: Pharmacophore mimetics

Q14. Which challenge is most relevant when formulating peptidomimetics for oral delivery?

• Excessive volatility during storage
• High susceptibility to gastric and intestinal enzymatic degradation
• Insufficient color intensity
• Incompatibility with saline

Correct Answer: High susceptibility to gastric and intestinal enzymatic degradation

Q15. Which analytical method is best suited for quantifying a peptidomimetic in biological matrices?

• UV–visible spectroscopy without separation
• LC–MS/MS (liquid chromatography–tandem mass spectrometry)
• Simple paper chromatography
• Infrared spectroscopy alone

Correct Answer: LC–MS/MS (liquid chromatography–tandem mass spectrometry)

Q16. Which statement correctly contrasts peptoids and peptides?

• Peptoids have side chains attached to the alpha carbon, identical to peptides
• Peptoids are oligomers of glycine only
• Peptoids have side chains attached to the nitrogen of the backbone, often increasing protease resistance
• Peptoids cannot adopt any secondary structure

Correct Answer: Peptoids have side chains attached to the nitrogen of the backbone, often increasing protease resistance

Q17. Which chemical modification is frequently employed to reduce peptide backbone flexibility and lock active conformation?

• Random alkylation of terminal groups
• Introduction of a methylene spacer between every residue
• Cyclization or incorporation of constrained amino acids
• Substitution with glycine-rich linkers

Correct Answer: Cyclization or incorporation of constrained amino acids

Q18. Which receptor interaction feature is most critical when designing a peptidomimetic agonist?

• Matching molecular weight only
• Reproducing key side-chain orientations and H-bonding interactions of the native peptide
• Eliminating all polar interactions
• Maximizing sequence length

Correct Answer: Reproducing key side-chain orientations and H-bonding interactions of the native peptide

Q19. Which of the following is a potential advantage of β-peptides over α-peptides?

• They are always water-insoluble
• They are more readily degraded by common proteases
• They can form stable noncanonical helices and resist proteolysis
• They cannot be synthesized by solid-phase methods

Correct Answer: They can form stable noncanonical helices and resist proteolysis

Q20. In the context of peptidomimetic drug discovery, what does “cellular target engagement” typically refer to?

• Measuring how much drug is present in the formulation container
• Demonstrating that the peptidomimetic binds its intended intracellular target and produces a pharmacodynamic effect
• Counting the number of cells in a culture
• Assessing only the in vitro solubility of the compound

Correct Answer: Demonstrating that the peptidomimetic binds its intended intracellular target and produces a pharmacodynamic effect

Download