The chloroalkane-bearing IP+ macrocycles (MPs 51-54) shown in Figure were synthesized, purified, and subjected to the CAPA using HEK293 cells stably expressing HTP. A Lipinski-compliant tryptophan-CA conjugate was used as a control for comparative purposes. These MPs are analogues of MP35, MP36, MP37 and MP40 (Figure ) but were constructed using Py25 (Figure ) to allow attachment of the CA tag to the secondary amine of the piperdine moiety. As shown in Figure , the IP+ MP-CA conjugates display CP50 values between 0.9 µM and 2.7 µM, whereas the Trp-CA Lipinski-compliant molecule displayed a CP50 value of 0.11 µM (see Supplementary Figures for the raw data). Thus, the MP-CA conjugates are approximately 8-to 25-fold less cell permeable than the Trp-CA control. We consider this to be a promising result given the much higher molecular masses of the MPs. A much more comprehensive analysis of the cell permeability of these MPs is underway and will be reported in due course.