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VHH fragments (nanobodies) are the smallest natural antigen-binding domains, derived from camelid heavy-chain-only antibodies.

Size

~15 kDa (smallest)

Origin

Camelids (llamas, camels)

Stability

Exceptional heat/pH resistance

Format

Single domain, no light chain

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Unique Features

VHH can access cryptic epitopes in protein cavities that larger antibodies cannot reach.
  • Extended CDR3 loops - Longer than conventional antibodies
  • No light chain pairing - Functions independently
  • Refolding capability - Can refold after denaturation
Requires specialized discovery platforms (camelid immunization or synthetic libraries).

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Applications

Excellent tissue penetration and low immunogenicity make VHH ideal for in vivo applications.
Can be expressed inside cells for intracellular target studies.
Stable under harsh conditions, ideal for robust assays.