Nanobodies: Chemical Functionalization Strategies and Intracellular Applications

Abstract

Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens.

Oral aktive Peptide: Gibt es ein Patentrezept?

“…Die nicht-invasive Einnahme von Insulin, das am weitesten verbreitete peptidische Medikament, steht nach wie vor im Zentrum der pharmazeutischen Forschung. [36] Der Übergang durch die Blut-Hirn-Schranke (blood-brain barrier, BBB) [37] wird hier ebenso wenig diskutiert wie zellpenetrierende Peptide, [38] gestapelte Peptide ("stapled peptides"), [39] Formulierungen [40] oder Nanotechnologien, die den peptidischen Wirkstofftransport verbessern. [35] Ein wichtiger Faktor fürd ie orale Verfügbarkeit ist die Formulierung der Wirkstoffe,die die Permeabilitäterheblich beeinflussen kann.…”

“…Das wird hier jedoch nicht ausführlicher besprochen, da zu diesem Thema erst kürzlich Reviews verçffentlicht wurden. [36] Der Übergang durch die Blut-Hirn-Schranke (blood-brain barrier, BBB) [37] wird hier ebenso wenig diskutiert wie zellpenetrierende Peptide, [38] gestapelte Peptide ("stapled peptides"), [39] Formulierungen [40] oder Nanotechnologien, die den peptidischen Wirkstofftransport verbessern. [41] Dieser Aufsatz beinhaltet die unterschiedlichen, bekannten Aufnahmemechanismen der intestinalen Bürstensaummembran, ausgenommen der Aufnahme über die orale oder nasale Mukosa, eine Vielzahl an Methoden, um die intestinale Permeabilitätz uu ntersuchen und den Einfluss zahlreicher chemischer Modifikationen auf die Bioverfügbarkeit, metabolische Stabilität, Bioaktivitätu nd Selektivitätv on Peptiden.…”

A Nanobody‐Conjugated DNA Nanoplatform for Targeted Platinum‐Drug Delivery

“…[17,18] After antigen recognition, Nbs can subsequently block signal transduction of at arget receptor to inhibit proliferation for combined therapy. [21] We hypothesized that functionalized Nbs may be used as aguidance system for adrug-loaded DNAn anocarrier. [21] We hypothesized that functionalized Nbs may be used as aguidance system for adrug-loaded DNAn anocarrier.…”

Orally Active Peptides: Is There a Magic Bullet?

“…Non-invasive administration of insulin, the most widely used peptide drug, has continuously been af ocus of pharmaceutical research. [36] Crossing of the blood-brain barrier (BBB) [37] is also not discussed here.F or further information about cell-penetrating peptides, [38] stapled peptides, [39] formulations, [40] or nanotechnologies to improve the transport of peptide drugs, [41] the reader is referred to the literature. [35] An important factor for oral availability is the drug formulation, which can strongly affect the permeability.T he permeability of the gut to the blood is also linked to cellular permeability,w hich is required to access an intracellular target.…”

“…However,t his will not be discussed here because reviews on this topic have recently been published. [36] Crossing of the blood-brain barrier (BBB) [37] is also not discussed here.F or further information about cell-penetrating peptides, [38] stapled peptides, [39] formulations, [40] or nanotechnologies to improve the transport of peptide drugs, [41] the reader is referred to the literature.…”