1 H NMR Titrations of SNAC. SNAC was dissolved in 0.7 mL CDCl3 containing 1% (v/v) TMS at concentrations ranging from 5 mM to 100 mM with gentle heating. Spectra were recorded immediately after the samples were dissolved on a Bruker NOE500-2 spectrometer for 32 scans at 298 K and all resonances were referenced to TMS as the internal standard. Clear concentrationdependent shifts (Supplementary Fig. ) of the amide (N-H) resonance in SNAC at ~6.3 ppm were observed, which is indicative of attractive supramolecular interactions dominated by hydrogen bonding (shown in Supplementary Fig. ) between the SNAC molecules in CDCl3 solution. The resulting 1 H NMR chemical shift-concentration plots (Supplementary Fig. ) were then analyzed with the with the Dynafit 66 (v 4.11.110) software package using a simple 1:1 homodimerization binding model for SNAC concentrations < 70 mM. However, for larger SNAC concentrations, clear deviations from a simple 1:1 binding model were observed, which is consistent with the formation of larger, dynamic SNAC aggregates that are also observed in DLS (Fig. ) and by all-atom molecular dynamics simulations (Fig. and Supplementary Fig. ). The DOSY pulse program used was a standard double-stimulated-echo experiment with bipolar gradient pulses and convection compensation (Pulse Sequence: dstebpg3s implemented in TopSpin). A total of 16 different spectra were recorded for all samples using a 98% pulse gradient for SNAC/SNAC and 69% pulse gradient for semaglutide, and data were processed in MestReNova (v 14.