The amino groups of hyperbranched polyethylenimine (HPEI) were partially modified with isobutyric anhydride to introduce isobutyramide (IBAm) groups to HPEI, resulting in an LCST-type thermoresponsive HPEI-IBAm that is positively-charged or neutral depending on the media pH. Succinic acid (SA) units were further introduced to HPEI-IBAm through acylation with succinic anhydride, resulting in the hyperbranched polyampholyte, HPEI-IBAm-SA, with both amino and carboxylic acid groups. H-1 NMR characterization proved the successful preparation of HPEI-IBAm-SA. Turbidimetry measurements showed that HPEI-IBAm-SA was also an LCST-type thermoresponsive polymer. The cloud point temperature (Tcp) of HPEI-IBAm-SA was pH-dependent. Compared with the HPEI-IBAm precursor, HPEI-IBAm-SA showed the thermoresponsive property in a wider pH range. At isoelectric point, HPEI-IBAm-SA had the lowest Tcp. The isoelectric point of HPEI-IBAm-SA could be tuned by controlling the amount of SA units, and the one with more SA units had a lower isoelectric point. Four halide anions with sodium as the counterion and four cations (Na+, K+, Mg2+ and Ca2+) with chloride as the counterion were used to measure the salt effects on the Tcp of HPEI-IBAm-SA. The specific ranking orderings of these ions in reducing the Tcp of HPEI-IBAm-SA were opposite at pH below and above isoelectric point. At pH above isoelectric point, the anion ranking is I- < Br- < Cl- < F-, and the cation ranking is Ca2+ > Mg2+ > Na+ approximate to K+. At pH below isoelectric point, and, the anion ranking is F- similar to Cl- < Br- < I- in the low-salt-concentration region (<= 10(-2) M), while the cation ranking is Na+ approximate to K+ > Mg2+ approximate to Ca2+. All the specific salt ordering found in HPEI-IBAm-SA system could be also found in the system of the protein representative, ovalbumin, implying that HPEI-IBAm-SA was a better protein model to mimic the interactions among ions and proteins with a different isoelectric point. (C) 2015 Elsevier Ltd. All rights reserved.